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1
Khurshid, Asma. "The effect of the polyadenylation inhibitor Cordycepin on MCF-7 cells." Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/28835/.
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Cordycepin (3′-deoxyadenosine) is a medicinal bioactive component of the caterpillar fungi (Cordyceps and Ophicordyceps). It is reported to have nephroprotective, antiapoptotic, anti-metastatic, hepatoprotective (Yue et al. 2013), inflammatory effects, antioxidant, anti-tumor, immunomodulatory and vasorelaxation activities. Cordycepin is well known to terminate and inhibit polyadenylation, both in vitro and in vivo. Other proposed mechanisms of action of cordycepin include activation of adenosine receptors, activation of AMP dependent kinase (AMPK) and inhibition of PARP1. The purpose of this study is to elucidate the biological and pharmacological effects of cordycepin on cancer cell lines such as MCF-7 cells. In this study I found that cordycepin reduces the cell proliferation in all examined cell lines without always exerting an effect on 4EBP phosphorylation and protein synthesis rates. Therefore, the effects on protein synthesis via inhibition of mTOR, which were previously reported, are not only the sole reason for the effect of cordycepin on cell proliferation. Knockdown of poly (A) polymerases reduces cell proliferation and survival, indicating that poly (A) polymerases are potential targets of cordycepin. I studied different adenosine analogues and found that 8 aminoadenosine, the only one that also consistently inhibits polyadenylation, also reduces levels of P-4EBP. It also inhibits the expression of specific genes indicating that the effects on polyadenylation, mTOR signalling and gene expression are linked. Also consistent with polyadenylation inhibition as the major mode of action is the fact that the effects of cordycepin on gene expression are predominantly post-transcriptional. However, knockdown of poly (A) polymerases did not have the same effects on gene expression or on polyadenylation, indicating that cordycepin may act as a dominant negative rather than as a null mutant. This is consistent with the fact that cordycepin is known to arrest a normally transient polyadenylation complex. We performed microarray analysis of cordycepin treated MCF-7 cells and found that the downregulated mRNAs were predominantly involved in transcriptional regulation, cell proliferation, cell cycle and cell migration. These data show that cordycepin is a promising new drug for cancer and indicates that the mode of action it is likely to be through the inhibition of polyadenylation.
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Eng, Jamei Raena. "Localization of anthracyclines in drug resistant human MCF-7 breast cancer cells." Thesis, University of Ottawa (Canada), 2007. http://hdl.handle.net/10393/27841.
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Multidrug resistance (MDR) commonly occurs during the treatment of cancer. Current research has focused mostly on the role of drug transporters, as the main mechanism of MDR; however, few have demonstrated a definite link between the expression or function of drug transporters and MDR in cancer patients.
Anthracyclines such as doxorubicin and epirubicin, autofluoresce and can be monitored by confocal microscopy. Two of the four resistant cell fines generated in our lab: the MCF-7EPI cells and to some extent MCF-7 DOX cells, exhibit a localization defect, whereby epirubicin is localized primarily in the cytoplasm rather than the nucleus. This drug localization defect temporally correlated with the onset of drug-resistance during selection for drug resistance in these cell lines. Consistent with the possible sequestration of drugs into acidic vesicles, acridine orange staining has revealed the presence of aggregates of acidified vesicles in the perinuclear region of MCF-7EPI cells. However, co-localization experiments using a number of intracellular organelle markers determined that epirubicin was localized to lysosomes and not consistently to acidic vesicles. An inhibitor of vacuolar H+ ATPase, was unable to restore the localization of epirubicin to the nucleus. Immunofluorescence using an ABCB1 antibody revealed the localization of ABCB1 predominantly in the plasma membrane and to some extent in the perinuclear region of MCF-7EPI cells. Nevertheless, inhibitors of this transporter failed to restore localization of epirubicin to the nucleus. Taken together, these findings strongly suggest that the acquisition of epirubicin resistance in breast tumour cells may involve the P-glycoprotein independent sequestration of drug into lysosomes. These lysosomes need not be acidic, nor does the removal of acid vesicles by inhibition of vacuolar H+ ATPases block the sequestration of drug into lysosomes.
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Pfeiffer, Thomas J. "Phytoestrogens may inhibit proliferation of MCF-7 cells, an estrogen-responsive breast adenocarcinoma cell line." Link to electronic thesis, 2004. http://www.wpi.edu/Pubs/ETD/Available/etd-0430104-132238.
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Tezcan, Okan. "Metastatic Behaviour Of Doxorubicin Resistant Mcf-7 Breast Cancer Cells After Vimentin Silencing." Master's thesis, METU, 2013. http://etd.lib.metu.edu.tr/upload/12615553/index.pdf.
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Chemotherapy is one of the common treatments in cancer therapy. The effectiveness of chemotherapy is limited by several factors one of which is the emergence of multidrug resistance (MDR). MDR is caused by the activity of diverse ATP binding cassette (ABC) transporters that pump drugs out of the cells. There are several drugs which have been used in treatment of cancer. One of them is doxorubicin that intercalates and inhibits DNA replication. However, doxorubicin has been found to cause development of MDR in tumors. It has been reported that there is a correlation between multidrug resistance and invasiveness of cancer cells. Vimentin is a type III intermediate filament protein that is expressed frequently in epithelial carcinomas correlating with invasiveness and also poor prognosis of cancer. There are several studies that have shown the connection between expression level of vimentin and invasiveness. In this study, MCF-7 cell line (MCF-7/S), which is a model cell line for human mammary carcinoma, and doxorubicin resistant MCF-7 cell line (MCF-7/Dox) were used. The resistant cell line was previously obtained by stepwise selection in our laboratory. The main purpose of this study was to investigate changes of metastatic behaviour in MCF-7/Dox cell line, after transient silencing of vimentin gene by siRNA. In conclusion, down-regulation of vimentin gene expression in MCF-7/Dox cell lines was expected to change the characteristics in migration and invasiveness shown by migration and invasion assays.
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Miazga, Natalie. "The effects of exogenous E-cadherin inhibition in MCF-7 mammary epithelial cells." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/the-effects-of-exogenous-ecadherin-inhibition-in-mcf7-mammary-epithelial-cells(e17fb558-8dcf-48ed-b095-5e28ea45c3b9).html.
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Understanding mechanisms that contribute to tumorigenesis and metastasis is important for developing more effective cancer therapies. Epithelial-mesenchymal transition (EMT) is associated with loss of the cell surface protein E-cadherin, increased tumour cell metastasis and acquisition of a cancer stem cell (CSC) phenotype. Whilst the process of EMT and aberrant E-cadherin expression during metastasis have been studied in detail, the role of exogenous inhibition of E-cadherin protein alone in epithelial cells remains to be elucidated. In this study the E-cadherin neutralising antibody SHE78.7 (nAb) and a peptide inhibitor of E-cadherin (nPep) have been used to assess how alterations in cell surface E-cadherin affect adenocarcinoma cell line MCF-7. MCF-7 cells exhibit an epithelial phenotype characterised by cell surface E-cadherin expression and lack of EMT marker expression, such as N-cadherin and Vimentin. Exogenous inhibition of cell surface E-cadherin using nAb in MCF-7 cells is a reversible process which induces increased cell numbers due to decreased apoptosis and cell proliferation. However, nAb treatment was insufficient to induce EMT or a CSC phenotype. Treatment of MCF-7 cells with nPep also induced increased cell numbers, but this was due to increased proliferation of the cells, with no changes in apoptosis observed. Microarray analysis of nAb-treated MCF-7 cells revealed >1000 gene transcript alterations compared to control Ab-treated cells, with changes associated with a wide range of cellular functions. Using an in silico network analysis approach, E-cadherin was identified as a positive regulator of the histone acetyltransferase p300. Exposure of MCF-7 cells to the p300 inhibitor garcinol resulted in increased CD44 and Slug, and decreased CD24 CSC associated transcripts. nPep treatment of MCF-7 cells and subsequent high content screening (HSC) analysis following exposure to a panel of cancer therapeutics demonstrated increased drug efficacy in combination with nPep for most of the therapeutics. Furthermore, nPep-treated MCF-7 cells exhibited a significantly altered plasma membrane-associated protein profile compared to control cells. Together, these results show that exogenous inhibition of E-cadherin in MCF-7 cells is a reversible event associated with increased proliferation, reduced apoptosis and significantly altered protein and transcript expression that may contribute to neoplasm formation in vivo. Furthermore, I show for the first time that inhibition of p300-dependent gene transactivation induces a CSC gene transcript expression profile in MCF-7 cells in vitro.
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Kanwal, Shahzina. "Effect of O-GlcNAcylation on tamoxifen sensitivity in breast cancer derived MCF-7 cells." Phd thesis, Université René Descartes - Paris V, 2013. http://tel.archives-ouvertes.fr/tel-00912341.
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One of the hallmarks of cancer cells is to exhibit increased uptake and consumption of glucose.3-5% of the glucose entering into the cell leads to a minor pathway of the glucose metabolismknown as the hexosamine biosynthetic pathway (HBP). UDP-N-acetylglucosamine is the endproduct of HBP and is used as substrate by OGT (O-GlcNAc transferase) to modify diverserange of nuclear and cytoplasmic proteins with a recently characterized post-translationalmodification called O-GlcNAcylation. It corresponds to the addition of sugar moiety O-linked β-N-acetylglucosamine (O-GlcNAc) on serine or threonine residue of proteins. This process isantagonized by another enzyme called O-GlcNAcase (OGA). Recent studies indicated thepresence of increased O-GlcNAcylation level in several cancer cells. Moreover, inhibition ofOGT has been shown to reduce in vivo and in vitro tumor growth of breast cancer cells.However, the relationship between O-GlcNAcylation and the response to anti-cancer therapy hasnot been studied. Tamoxifen is the oldest and most prescribed selective-estrogen receptormodulator (SERM) for patients with estrogen receptor (ER)-positive breast cancer. Tamoxifen isknown to reduce tumor growth and invasion. Despite its beneficial effects de novo and acquiredresistance are great obstacles in its clinical effectiveness. We found that O-GlcNAc elevation inMCF-7 cells protected them from tamoxifen-induced cell death. Increased O-GlcNAc alsoincreased PI3-K/Akt signaling. However, the protective effect of PUGNAc+glucosamine fromtamoxifen-induced cell death is independent of PI3K/Akt pathway. Increased O-GlcNAcylationalso led to reduced ESR1 promoter activity and decreased expression of ERα at mRNA andprotein levels. The decrease in ERα expression is correlated with a reduced expression of twotamoxifen regulated genes i.e. early growth response 1 and p21 Waf1/Cip1. In conclusion, thisstudy showed for the first time the involvement of O-GlcNAcylation in reducing tamoxifen142sensitivity in MCF-7 cells. Thus, OGT can act as a novel therapeutic target for treatment oftamoxifen resistant cells.
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Qattan, A. T. M. "Large scale quantitative organelle proteomics of protein distribution in breast cancer MCF-7 cells." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1415963/.
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This thesis analyzes the dynamic complexity involved in the subcellular distribution of the proteins for the malignant breast epithelial MCF-7 cell line, using mass spectrometry based quantitative proteomics for the indirect measurement of the subcellular dispersion of the constituent proteins of core cellular functions. The thesis demonstrates that there are many proteins which can be present in more than one subcellular organelle. Quantitative proteomics using LFQP (Label-Free Quantitative Proteomics) methodology based on mass spectrometry was shown to be suitable for the indirect measurement of the distribution of the proteins in the malignant breast epithelial cell line. The study used partial purification by means of dynamic sucrose gradient centrifugation to avoid the need of multiple purification procedures for different organelles and loss of proteins during purification. This was followed by proteomics identification and analysis of the protein content from the sucrose gradient fractions corresponding to the major organellar compartment. These included the nucleus, cytosol, mitochondria, plasma membrane and endoplasmi c reti cul um. The first part of the thesis indicates that 50.00% - 75.00% of the proteins detected showed multiple-locations. Out of the total quantified proteome using LFQP methodology, 2184 proteins were securely identified. 481 proteins (22.00%) were found in unique sucrose gradient fractions which suggest that they may have unique locations, while 454 proteins (20.80%) were found to be ubiquitously distributed and the remaining 1249 proteins (57.20%) were consistent with intermediate distribution over multiple locations. 94 proteins implicated in breast cancer and 478 other proteins which share the same major cellular biological processes with most of the breast cancer proteins were observed in 334 and 1223 subcellular locations respectively. The second part of the thesis concentrates on the spatial distribution of proteins between two organelles of particular interest for cancer: the nucleus and mitochondria. Two important characteristics of cancer cellular function include high degrees of genetic instability and major changes in cellular energy metabolism. The genetic instability, which is associated with the cell nucleus, allows cells to escape from a variety of normal restrictions on proliferation, whereas the changes in energy metabolism are associated with mitochondria and the need for new cellular components to be produced in the proliferating cells. The large scale proteomics analysis of the partitioning of proteins between mitochondria and the nucleus reveals that 40.00% of all the proteins were shared between the mitochondria and the nucleus. The observed partitioning of these proteins between these two organelles showed a functional distribution which is consistent with the first part of the thesis. The analysis of the distribution between the nucleus and mitochondria of specific subgroups of the proteins involved in oxidative phosphorylation, the tricarboxylic acid cycle, RNA processing/translation, glycolysis and Ras-related signalling suggests that the spatial distribution of numerous proteins over multiple sites is critical to cellular function and that there are unrecognized aspects of functional coordination between the mitochondria and the nuclei which need further investigation. In addition, the large number of proteins identified to be in multiple locations indicates that subcellular spatial integration of function may be a vital aspect of cancer. The findings in this study also reveal that most of the observed proteins with multiple subcellular locations had current annotations of location which are still sparse in public databases. In general terms, the extensive subcellular dispersion of the constitute proteins of core cellular functions may be a fundamental feature of the cell which may be constituent with the requirements for robustness in a complex system.
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Wood, Rachel. "The effects of JNK isoform knockdown on cell growth and death in HUVECs and MCF-7 cells." Thesis, University of Strathclyde, 2017. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=27904.
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Cardiovascular disease (CVD) and cancer are two of the leading causes of mortality worldwide. The JNK pathway has been shown to play key roles at various stages of both of these diseases and therefore is an important protein to try and understand. In animal models of atherosclerosis and breast cancer, inhibition of JNK has been demonstrated to reduce pathogenesis and therefore targeting this protein may be key for developing treatments. JNK exists as three individual proteins, JNK1, JNK2 and JNK3 and studies are now showing that not only can these proteins work independently but also opposingly in some instances and therefore understanding the function of the individual isoforms is becoming critical to fully understanding this pathway. Although more research is focusing on JNK isoform function, characterisation of each JNK protein has not yet been carried out in human primary vascular cells or a human breast cancer cell line, an investigation which must be carried out to understand the role of this pathway in the pathogenesis of these diseases. In the current study lentiviral shRNA was used to target and knockdown JNK1 and JNK2 in both human umbilical vein endothelial cells (HUVECs) and MCF-7 breast cancer cells and the effects of knockdown on cell growth and cell death processes were analysed. In HUVECs knockdown of JNK2 caused an increase in pc-Jun levels and an increase in the percentage of multinucleated cells was observed, suggesting JNK2 may play a role in HUVEC cell growth. Unfortunately, the lentiviral infection itself caused detrimental effects which made it difficult to continue experiments and explore these findings further. In MCF-7 cells JNK knockdown did not produce any changes in cell growth or induced cell death when compared to non-target controls, suggesting that JNK does not play a key role in this breast cancer cell line.
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Fix, Lindsey Zhang Baohong. "Effect of green tea Polyphenon 60 on microRNA expression in MCF-7 breast cancer cells." [Greenville, N.C.] : East Carolina University, 2010. http://hdl.handle.net/10342/2725.
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Husbeck, Bryan. "Changes in gene expression induced by thioredoxin-1 in MCF-7 human breast cancer cells." Diss., The University of Arizona, 2002. http://hdl.handle.net/10150/280113.
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Thioredoxin-1 (Trx-1) is a small redox protein that is overexpressed in a number of human cancers. Elevated levels of Trx-1 in tumors is associated with increased cell proliferation, decreased apoptosis, and decreased patient survival. However, the mechanism(s) for the growth stimulating and anti-apoptosis effects of Trx-1 are unknown. We used DNA microarray technology to identify genes whose expression was altered in MCF-7 breast cancer cells stably transfected with wild-type Trx-1 (MCF-7/Trx 9) or a redox inactive mutant Trx-1 (MCF-7/SerB 4) compared to empty-vector transfected cells (MCF-7/neo). The expression of cytochrome P450 1B1 (CYP1B1) mRNA and protein is increased by Trx-1 transfection of MCF-7 human breast cancer cells and decreased by a redox inactive mutant Trx-1. CYP1B1 is a tumor specific CYP which converts 17β-estradiol (E₂) to the carcinogenic 4-hydroxyestradiol (4-OHE₂). The expression of peroxiredoxin 1 (PRDX1) mRNA is increased as a result of Trx-1 overexpression in MCF-7 cells. The peroxiredoxins belong to a conserved family of antioxidant proteins that use thiol groups as reducing equivalents to scavenge oxidants. Transfection of mouse WEHI7.2 thymoma cells with human PRDX1 protects cells from apoptosis induced by H₂O₂. Spermine/spermidine N'-acetyltransferase (SSAT) mRNA expression and enzyme activity is decreased by Trx-1 transfection of MCF-7 human breast cancer cells. SSAT is an important enzyme in the polyamine catabolic pathway. The inhibition of SSAT enzyme activity is associated with decreased putrescine levels in the Trx-1 transfected cells. Therefore, it appears as if the modification of cellular redox signaling brought about by the overexpression of Trx-1 in breast cancer cells induces changes in gene expression that contribute to the transformed phenotype. Trx-1 redirects estrogen metabolism in a more toxic pathway due to the induction of CYP1B1, provides resistance to apoptosis induced by reactive oxygen species via the upregulation of PRDX1, and alters polyamine metabolism by inhibiting the expression of SSAT.
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Webber, Kristie Elmslie. "Studies on the Effects of Paraben Mixtures on MCF-7 Breast Cancer Cells in Culture." Thesis, University of Canterbury. Department of Chemistry, 2013. http://hdl.handle.net/10092/8677.
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Parabens are the esters of p-hydroxybenzoic acid and are commonly used as preservatives in personal care products, pharmaceutical preparations and cosmetics. Recently parabens have been found to be estrogenic, bringing into question if exposure to them is adversely affecting human health. Given exposure to multiple xenoestrogens is constant; research has been carried out to determine what effect combinations of xenoestrogens might have on human and environmental health. Parabens are almost always present in combinations in formulae as this increases their antimicrobial activity, so it is important to know what the effect of this is. The main aim of this study was to determine what the effect of combining methylparaben and butylparaben together has on the proliferation of MCF-7 breast cancer cells, which proliferate in the presence of estrogen. This study was carried out by exposing MCF-7 breast cancer cells to combinations of methylparaben and butylparaben and measuring cell proliferation by counting cells using a cytometer. The results show that butylparaben caused a greater increase in cell proliferation compared to methylparaben. When methylparaben and butylparaben were combined together, the resulting cell proliferation was greater than the cell proliferation produced by either methylparaben or butylparaben alone at a concentration twice the amount of either paraben concentration contained within the mixture. These results were analysed using Analysis of Variance, which determined the combination treatments were statistically different from the single treatments according to Fishers method. This suggests that there is a synergistic effect produced when methylparaben and butylparaben are combined together, however large variation and dose dependent discrepancies means this result is uncertain and further studies need to be carried out.
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Miranda, Juliana Xavier de. "Efeitos do tratamento com selênio no crescimento e marcas epigenéticas de células de adenocarcinoma mamário humano MCF-7." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/9/9132/tde-11032013-090654/.
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O câncer de mama representa problema mundial de saúde pública e a causa mais frequente de morte por câncer entre as mulheres. A identificação de agentes moduladores de marcas epigenéticas, tais como metilação global do DNA e modificações pós-tradução em histonas, compreende alternativa promissora para estabelecimento de estratégias de controle da carcinogênese mamária. Dentre os nutrientes, o elemento traço essencial selênio (Se) pode ser destacado como agente dietético com potencial anti-câncer de mama e que poderia atuar modulando processos epigenéticos. Entretanto seus mecanismos de ação são pouco elucidados. Este estudo objetivou, assim, identificar efeitos do tratamento com selênio no crescimento e marcas epigenéticas de células de adenocarcinoma mamário humano MCF-7. Células MCF-7, positivas para o receptor de estrógeno, foram tratadas com ácido metilselenínico (MSA) ou selenito de sódio (ST) por diferentes tempos e em diferentes concentrações. Foram avaliados: padrão de proliferação (ensaio cristal violeta) e viabilidade celular (método de exclusão azul de tripan); integridade de membrana plasmática (citometria de fluxo); níveis de fragmentação do DNA (citometria de fluxo), distribuição das fases do ciclo celular (citometria de fluxo); apoptose (citometria de fluxo/ marcação dupla com Anexina V - Iodeto de propídio); níveis de lisina 9 acetilada (H3K9ac) e trimetilada (H3K9me3) em histona H3; níveis de lisina 16 acetilada (H4K16ac) em histona H4 (Western blot); padrão de metilação global do DNA (HPLC-DAD); expressão de gene supressor de tumor (RASSF1a; qPCR) e padrão de metilação da região promotora (RASSF1a e RARβ; MS-PCR); expressão da enzima DNA metilstransferase 1 (DNMT1) (Western Blotting). Comparado ao grupo controle de células não tratadas (GC), ambos os tratamentos com MSA ou ST inibiram a proliferação e viabilidade de células MCF-7 de forma dose e tempo dependente. Ambas as formas químicas de Se induziram a parada do ciclo celular, aumentando (p< 0,05) a proporção de células na fase G2/M e reduzindo (p< 0,05) a proporção daquelas nas fases G0/G1 e S. Os tratamentos com MSA favoreceram a morte celular por apoptose, que foi associada com nível de fragmentação de DNA aumentado (p< 0,05), e reduzida ruptura da membrana plasmática associada com a exposição aumentada (p< 0,05) de fostadilserina. Por outro lado, o ST aumentou (p< 0,05) a fragmentação do DNA e (p< 0,05) a positividade ao iodeto de propídio associado à indução de necrose (p< 0,05). Dentre os mecanismos epigenéticos investigados, 1,6µM e 2µM reduziram a acetilação de H3K9ac (72h; p< 0,05) e aumentaram a de H4K16ac (96h; p< 0,05). O tratamento por 96h com 2µM de MSA reduziu (p< 0,05) a metilação de H3K9me3. Ambos MSA e ST não alteraram o padrão de metilação global do DNA, mas reduziram a expressão de DNMT1, após 96h com 2µM de MSA (p< 0,001; 88%) e após 120h com 10µM de ST (p< 0,001; 96%). ST, mas não o MSA, aumentou (p< 0,05; 45%) a expressão do gene RASSF1a. Em ambos os grupos tratados com MSA ou ST, bem como no GC, a região promotora dos genes RASSF1a e RAR estavam predominantemente metiladas. Estes resultados fornecem evidências de que as ações anti-câncer de mama de compostos do selênio dependem de sua forma química. Além disso, a modulação de processos epigenéticos parecem ser relevantes para as ações inibitórias do MSA em células de câncer de mama.Breast cancer is a global public health problem and the most frequent cause of cancer death among women. The identification of agents able to modulate epigenetic marks, such as global DNA methylation and histone post-translational modifications, comprises promising alternative for establishing control strategies on mammary carcinogenesis. Among the nutrients, the essential trace element selenium (Se) can be highlighted as a dietary agent with potential anti-breast cancer and could act by modulating epigenetic processes. However its mechanisms of action are poorly understood. This study aimed, therefore, to identify the effects of selenium treatment on growth and epigenetic marks of MCF-7 human breast adenocarcinoma cells. MCF-7 cells, positive for estrogen receptor, were treated with methylseleninic acid (MSA) or sodium selenite (ST) for different times and in different concentrations. Evaluated parameters included: cell proliferation (crystal violet assay) and cell viability (trypan blue exclusion assay); plasma membrane integrity (flow cytometry); levels of DNA fragmentation (flow cytometry), apoptosis (flow cytometry - double labeling with Annexin V - propidium iodide); distribution of cell cycle phases (flow cytometry); acetylated (H3K9ac) and trimethylated (H3K9me3) lysine 9 levels on histone H3; acetylated (H4K16ac) lysine 16 level on histone H4 (Western blot); global DNA methylation (HPLC-DAD); tumor suppressor gene expression (RASSF1a; qPCR) and promoter methylation (RASSF1a, RARβ; MS-PCR); DNA methyltransferase 1 (DNMT1) expression (Western blot). Compared to untreated cells (controls), both MSA and ST inhibited (p< 0.05) MCF-7 cell proliferation and viability in a dose- and time-dependent manner. Treatments with MSA favored cell death by apoptosis, that was associated with increased (p< 0.05) DNA fragmentation level, reduced plasma membrane rupture associated with high (p< 0.05) phosphatidylserine exposure. On the other hand, ST increased (p< 0.05) DNA fragmentation, enhanced (p< 0.05) propidium iodide positivity associated to necrosis induction (p< 0,05). Both chemical forms of Se induced nduced cell cycle arrest, increasing (p< 0.05) the proportion of cells in G2/M phase and reducing (p< 0.05) the proportion of those in G0/G1 and S phases. Among the epigenetic mechanisms investigated, 1.6µM and 2µM of MSA reduced acetylation of H3K9ac (72h, p< 0.05) and increased the H4K16ac (96h, p< 0.05). The treatment for 96h with 2µM of MSA reduced (p< 0.05) the H3K9me3 methylation. Neither MSA nor ST altered (p> 0.05) global DNA methylation, while both compounds reduced (p< 0.05) DNMT1 protein expression, after 96h with 2µM of MSA (p< 0.001; 88%) and after 120h with 10µm of ST (p< 0.001; 94%). ST, but not MSA, increased (p< 0.05; 45%) RASSF1a gene expression. In control and Se-treated cells promoter regions of RASSF1a and RARβ were predominantly methylated. These results provide evidence that the anti-breast cancer actions of selenium compounds depend on its chemical form. Additionally, modulation of epigenetic processes seems to represent a relevant feature of MSA inhibitory effects in breast cancer cells.
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Xu, Yan 1958. "Human protein tyrosine phosphatase SHP-1 : gene regulation and role in apoptosis in MCF-7 cells." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38441.
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SHP-1, a SH2 domain-containing protein-tyrosine phosphatase, plays a critical role in regulation of cell signal transduction. SHP-1 is expressed not only in cells of hematopoietic lineages, but also in many non-hematopoietic cells under the control of a tissue-specific promoter, P1. In the first part of this thesis, the activity of the P1 promoter was analyzed in a region spanning 3.5 kb upstream of the major transcription start site in non-hematopoietic MCF-7 cells. An upstream Sp1 element (-126 to -118) positively regulated this TATA-box-lacking promoter. Two inverted CCAAT-elements (-332 to -328 and -66 to -62) played the important, but opposite roles, and transcription factor NF-Y predominantly bound to the two CCAAT-elements to control SHP-1 gene expression. Furthermore, incubation of MCF7 cells with 100 ng/ml trichostatin A (TSA), an inhibitor of histone deacetylase, significantly increased the activity of the P1 promoter. Mutation in the proximal CCAAT-element, however, eliminated the activating effect of trichostatin A on the promoter. In the second part of this thesis, the mechanism by which SHP-1 modulated TSA-induced MCF-7 cell apoptosis was elucidated. Analysis of cell survival signaling pathways revealed that overexpression of SHP-1 inactivated Akt ( eg. diminished phosphorylation resulted from modulation of PI3K expression) and increased caspase-9 and caspase-7 activities. Interestingly, a parallel decrease was observed in the phosphorylation of the pro-apoptosic Bcl-2 family member Bad at Ser112 as well as in the stress-activated MAP kinase JNK, both of which have been implicated in Akt- as well as ERK1/2-mediated functions. It was not surprising, therefore, to detect a diminished level of phosphorylated ERK1/2 in SHP-1-overexpressiog cells and that this effect was exacerbated by TSA treatment. Taken together, the data presented in this thesis suggest that SHP-1 expression is regulated by Sp1 and NF-Y factors, and SHP-1 sensitizes MCF-7 cells to TS
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Zhang, Hua-Tang. "Transfection of angiogenic factors into human MCF-7 breast carcinoma cells : effects on growth in vivo." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308606.
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Alkhanjaf, A. A. M. "Proteomics of sub-cellular protein distribution in oestrogen and tamoxifen stimulated MCF-7 breast cancer cells." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1517967/.
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Hormone receptor positive (HR+) breast cancer represent 70% of all breast tumours. Its oncogenesis is multiple step process thought to be driven by the presence of two transcription factors, the oestrogen receptor (ER) and/or the progesterone receptor (PR). Therefore, the endocrine-targeted therapeutic approach has been focused on both receptors as prognostic markers and therapeutic targets, aiming to alter the oestrogen signalling for patients with ERα-positive disease. The benefits gained from the treatment appear to be limited by developing either de novo or acquired resistance following a period of response to tamoxifen. In the present work, global quantitative proteomics was combined with the analysis of fractions enriched in target subcellular locations (nuclear and cytoplasmic fractions), this has allowed measurement of the changes in total abundance and in the compartmental abundance/distribution between the nucleus and cytoplasm for several thousand proteins differentially expressed in MCF-7cells in response to oestrogen and tamoxifen stimulation in MCF-7 cells. In the first part of the thesis, we have used a proteomics subcellular spatial razor approach to look at changes in total protein abundance and in protein distribution between the nucleus and cytoplasm following exposure of MCF7 breast cancer cells to oestradiol. The dominant response of MCF7 cells to oestrogen stimulation involves dynamic changes in protein subcellular spatial distribution rather than changes in total protein abundance. Of the 3604 quantitatively monitored proteins, only about 2% show substantial changes in total abundance (>2-fold), whereas about 20% of the proteins show substantial changes in local abundance and/or redistribution of their subcellular location, with up to 16-fold changes in their local concentration in the nucleus or the cytoplasm. The second part of the thesis focuses on the spatial distribution of proteins in the three sub-proteome fractions (total lysate, nuclear and cytoplasmic fractions) in 4-OHT stimulated MCF-7 cells. Of the 3493 quantitatively monitored proteins, 97 of quantified proteins were detected as a core data set with differential abundance (DA) that was significantly changed in total abundance and/or subcellular location (P < 0.05). More than 50% of the proteins show significant changes in local abundance and/or redistribution of their subcellular location, only 19 proteins show substantial changes in the total lysate. Following the rigorous downstream analysis of the pathways significantly overrepresented and GO terms significantly enriched, this analysis showed that protein changes in abundance with 4-OHT across multiple sample types (CNT) were involved in pathways related to metabolism, signal transduction, growth and proliferation, and development. The nuclear response involved upregulation of the proteins participating in the GPCR downstream signalling pathway leading to accumulated response in the cancer pathway by moderately modulating the cell survival (PI3K/AKT) pathway in a circadian rhythm. Furthermore, this was accompanied by substantial changes in the local abundance and /or the redistribution of the metastasis mediating proteins and apoptotic cleavages of cell adhesion proteins. We propose that dynamic redistribution of the subcellular location of multiple proteins in response to stimuli is a fundamental characteristic of cells and suggest that perturbation of cellular spatial control may be an important feature of cancer.
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Amaral, Jonatas Bussador do. "Células MCF-7 como modelo 3D no estudo de câncer de mama humano." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-21072011-134443/.
Full textAbstract:
O diferencial da cultura de células em 3-dimensões é permitir que as células explorem as 3-dimensões do espaço, aumentando assim as interações com o ambiente e entre as células. Em estudos relacionados à biologia do câncer de mama, vem ganhando espaço a utilização de esferóides para estudos que visam à compreensão da morfogênese do espaço luminal. Neste trabalho foi mostrado que as células MCF-7 reorganizam-se em estruturas tubulares e acinares. Em ambas as situações, a formação do lúmen veio acompanhada pelo estabelecimento de uma camada de células polarizadas, arranjo este muito semelhante ao encontrado em glândulas mamárias. Os resultados apresentados apontam para a existência de uma população de células na linhagem MCF-7 que não estão totalmente comprometidas ao fenótipo tumoral. Mantidos diferenciados, os esferóides de células MCF-7 apontam como um novo modelo para estudos relacionados à formação do lúmen, permitindo assim explorar o papel de diferentes vias como as relacionadas a apoptose, autofagia, diferenciação e sobrevivência celular.As a particularity, a 3D cell culture permits cells to explore the three dimensions of the space thereby increasing cell-cell interactions, as well as interaction with the environment. In studies related to breast cancer biology, spheroids are becoming widely used in the aim to comprehend luminal space morphogenesis. We showed that MCF-7 cells reorganize themselves in tubular and acinar structures. In both situations, lumen formation was accompanied by the establishment of a layer of polarized cells, an arrangement that is very similar to that of breast glands. The presented results suggest the existence of an MCF cell line population not completely committed to the tumor phenotype. When maintained as differentiated, MCF-7 cell spheroids can be a new model for studies regarding lumen formation, thereby exploring the role of diiferent pathways, such as those related to cell apoptosis, autophagy, differentiation and survival.
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Donmez, Yaprak. "Reversal Of Multidrug Resistance By Small Interfering Rnas (sirna) In Doxorubicin Resistant Mcf-7 Breast Cancer Cells." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/3/12611496/index.pdf.
Full textAbstract:
Resistance to anticancer drugs is a serious obstacle to cancer chemotherapy. A common form of multidrug resistance (MDR) is caused by the overexpression of transmembrane transporter proteins P-glycoprotein and MRP1, encoded by MDR1 and MRP1 genes, respectively. These proteins lead to reduced intracellular drug concentration and decreased cytotoxicity by means of their ability to pump the drugs out of the cells. Breast cancer tumor resistance is mainly associated with overexpression of P-gp/MDR1. Although some chemical MDR modulators aim to overcome MDR by impairing the function of P-gp, they exhibit severe toxicities limiting their clinical relevance. Consequently, selective blocking of the expression of P-gp/MDR1 specific mRNA through RNA interference strategy may be an efficient tool to reverse MDR phenotype and increase the success of chemotherapy.
Aim of this study was re-sensitizing doxorubicin resistant breast cancer cells to anticancer agent doxorubicin by selective downregulation of P-gp/MDR1 mRNA. The effect of the selected MDR1 siRNA and MRP1 expression after MDR1 silencing was determined by qPCR analysis. XTT cell proliferation assay was performed to
v
determine the effect of MDR1 silencing on doxorubicin sensitivity.Intracellular drug accumulation and localization was investigated by confocal laser scanning microscopy after treatment with MDR1 siRNA or other MDR modulatorsverapamil or promethazine. The role of P-gp in migration characteristics of resistant cells was evaluated by wound healing assay. The results demonstrated that approximately 90% gene silencing occurred by the selected siRNA targeting MDR1 mRNA. However the level of MRP1 mRNA did not change after MDR1 downregulation. Introduction of siRNA resulted in about 70% re-sensitization to doxorubicin. Silencing of P-gp encoding MDR1 gene resulted in almost complete restoration of the intracellular doxorubicin accumulation and re-localization of the drug to the nuclei. Despite the considerably high concentration of the modulators, verapamil and promethazine were not as effective as siRNA for reversal of the drug efflux. According to wound healing assay, MDR1 silencing did not have any effect on migration characteristics of resistant cells, that is, P-gp expression does not seem to affect the motility of the cells. Selected siRNA duplex was shown to effectively inhibit MDR1 gene expression, restore doxorubicin accumulation and localization, and enhance chemo-sensitivity of resistant cells, which makes it a suitable future candidate for therapeutic applications.
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Parrish, Pamela Ruth 1965. "Decreased intracellular mitoxantrone in resistant MCF-7 breast cancer cells is attributed to an energy dependent efflux." Thesis, The University of Arizona, 1990. http://hdl.handle.net/10150/278582.
Full textAbstract:
Intracellular drug accumulation was studied in two drug resistant variants of the human breast cancer MCF-7 (MCF/7) cell line selected with mitoxantrone (MCF7/Mitox) and doxorubicin (MCF7/D40). Earlier studies show that both cell lines have similar cell cycle characteristics, and both are multidrug resistant. Previously, P-glycoprotein was detected in MCF7/D40, but not in MCF7/Mitox. Both cell lines, however, display decreased drug accumulation. The P-glycoprotein chemo-modulator verapamil increased mitoxantrone accumulation 1.6 fold in MCF7/D40 cells, thus achieving identical intracellular drug levels to the MCF7/S cell line. Verapamil had little effect on drug accumulation in MCF7/Mitox cells. Rapid influx of mitoxantrone from 5 seconds to 60 seconds was not significantly different between MCF7/Mitox and MCF7/S. Influx in the MCF7/D40 cell line was greater than in the MCF7/Mitox or MCF7/S cell lines. Decreased drug accumulation was found to be at least partly due to enhanced drug efflux. Depletion of 73.9% to 88.9% of cellular ATP by sodium azide (NaN3) decreased the efflux of mitoxantrone in each cell line, thus demonstrating an energy dependence of drug efflux.
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Strong, Rachael F. "A comparative proteomic analysis of mitochondrial proteins from drug susceptible and drug resistant human MCF-7 breast cancer cells." College Park, Md. : University of Maryland, 2005. http://hdl.handle.net/1903/2870.
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Keskin, Tugba. "Preparation Of Polyethylene Glycol Coated Magnetic Nanoparticles For Targeting Of Cancer Cells." Master's thesis, METU, 2012. http://etd.lib.metu.edu.tr/upload/12614089/index.pdf.
Full textAbstract:
Conventional cancer chemotherapies cannot differentiate between healthy and cancer cells, and lead to severe side effects and systemic toxicity. In the last decades, different kinds of controlled drug delivery systems have been developed to overcome these shortcomings of chemotherapeutics. Magnetic nanoparticles (MNP) are potentially important in cancer treatment since they can be targeted to tumor site by an externally applied magnetic field.
In this study, it is aimed to synthesize folic acid conjugatedpolyethylene glycol (PEG) coated magnetic nanoparticles with appropriate size, surface chemistry, magnetization and biocompatibility to be used in biomedical applications. First MNP were synthesized, then covered with oleic and PEG
and finally conjugated with folic acid. A detailed characterization of synthesized nanoparticles was done by TEM, XRD, FTIR, VSM and XTT analyses. MNP synthesized by the rapid addition of ammonium hydroxide exhibited more spherical nanoparticles with a narrower size distribution. Agglomeration tendency of naked nanoparticles was prevented by oleic acid addition during the synthesis. Both naked and surface treated MNP have been found to exhibit superparamagnetic behavior both at room temperature (23
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Mankame, Tanmayi Pradeep. "Evaluation of alterations in gene expression in MCF-7 cells induced by the agricultural chemicals Enable and Diazinon." Thesis, Texas A&M University, 2003. http://hdl.handle.net/1969.1/2233.
Full textAbstract:
Steroid hormones, such as estrogen, are produced in one tissue and carried through the blood stream to target tissues in which they bind to highly specific nuclear receptors and trigger changes in gene expression and metabolism. Industrial chemicals, such as bisphenol A and many agricultural chemicals, including permethrin and fervalerate, are known to have estrogenic potential and therefore are estrogen mimics. Widely used agricultural chemicals, Enable (fungicide) and Diazinon (insecticide), were evaluated to examine their toxicity and estrogenicity. MCF-7 cells, an estrogen-dependent human breast cancer line, were utilized for this purpose. MCF-7 cells were treated with 0.033-3.3 ppb (ng/ml) of Enable and 0.3-67 ppm of Diazinon and gene expression was compared to that in untreated cells. Microarray analysis showed down-regulation of eight genes and up-regulation of thirty four genes in cells treated with 3.3 ppb of Enable, compared to untreated cells. Similarly, in cells treated with 67 ppm of Diazinon, there were three genes down-regulated and twenty seven genes up-regulated. For both chemicals, specific genes were selected for special consideration. RT-PCR confirmed results obtained from analysis of the microarray. These studies were designed to provide base-line data on gene expression-altering capacity of specific chemicals and will allow assessment of the deleterious effects caused by exposure to the aforementioned chemicals.
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Teixeira, Christine. "Characterization of the molecular mechanisms underlying retinoic acid induced growth inhibition in MCF-7 human breast cancer cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0015/NQ46549.pdf.
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Fu, Zongming. "Comparative proteomics studies of soluble nuclear proteins of drug susceptible and resistant human breast cancer MCF-7 cells." College Park, Md. : University of Maryland, 2004. http://hdl.handle.net/1903/1945.
Full textAbstract:
Thesis (Ph. D.)--University of Maryland, College Park, 2004.Thesis research directed by: Chemistry. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Budworth, Joanna. "Effects of inhibitors of protein kinase C in drug sensitive and multidrug resistant Mcf-7 breast carcinoma cells." Thesis, University of Leicester, 1996. http://hdl.handle.net/2381/34288.
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Xu, Tongtong. "Study of anti-cancer effect of winter worm and summer grass on Mcf-7 human breast cancer cells." Diss., Columbia, Mo. : University of Missouri-Columbia, 2008. http://hdl.handle.net/10355/5619.
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Thesis (M.S.)--University of Missouri-Columbia, 2008.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on July 9, 2009) Includes bibliographical references.
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Zhu, Weiwei. "Effects of Membrane Lateral Organization on the Anticancer Activity of Liposomal CA4P against MCF-7 Breast Cancer Cells." Master's thesis, Temple University Libraries, 2010. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/87353.
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BiochemistryM.S.
The goal of this research is to study how the cholesterol content in liposomal formulations affects the anticancer activity (e.g., cell growth suppression) of combretastatin A4 phosphate (CA4P). CA4P is a powerful antivascular agent currently under clinical trials for treating solid tumors. Liposomal CA4P has several advantages over free CA4P, including the reduced toxicities and the increased overall drug efficacy. In this thesis work, I have demonstrated that the proliferation of breast cancer MCF-7 cells varies with the cholesterol mole fraction in the formulation of liposomal CA4P in a biphasic manner, displaying a local minimum at the critical sterol mole fractions (Cr) for maximal superlattice formation. Cell proliferation was monitored using a fluorescence-based assay. Since cholesterol content determines membrane lateral organization, my results imply that membrane lateral organization plays an important role in regulating the anti-cancer activity of liposomal CA4P. This finding provides a new concept in the rational design of liposomal anti-cancer drugs. More than 20 anticancer drug formulations are in the market or under clinical trials. Most of them include cholesterol as a major component. My present study indicates that cholesterol is not just serving as a vesicle stabilizing agent, but also modulates the activity of liposomal drugs. The principle learned from CA4P can be extended to other liposomal anti-cancer drugs. This study is also significant from the membrane biophysics point of view. The data provide additional support for the sterol superlattice model and illustrate that the concept of sterol superlattice can be applied to biotechnology development.
Temple University--Theses
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Pedro, Rafael de Oliveira. "Desenvolvimento de sistemas anfifílicos baseados em derivados de quitosana para transporte e liberação sustentada de fármacos." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/75/75134/tde-25052017-101542/.
Full textAbstract:
Esse trabalho apresenta resultados de modificações estruturais, caracterizações e aplicações de derivados de quitosana como carreadores de fármacos. Derivados anfifílicos de quitosana, contendo grupos hidrofílicos e grupos hidrofóbicos, foram caracterizados por técnicas de espectroscopia de ressonância magnética nuclear (RMN1H), espectroscopia na região do infravermelho (IV), espectroscopia na região do UV-Vis, técnicas termoanalíticas (termogravimetria (TGA), termogravimetria derivada (DTG), análise térmica diferencial (DTA) e calorimetria exploratória diferencial (DSC)), fluorescência no estado estacionário, espalhamento dinâmico de luz (DLS) e microscopia eletrônica de transmissão (MET). Os resultados de caracterização mostraram que as sínteses propostas foram realizadas com sucesso. A determinação da concentração de agregação crítica (CAC) e os estudos de DLS e MET confirmam que os derivados se auto-organizam em solução aquosa formando agregados com diâmetros variando entre 230 a 500 nm. Esses valores, associados aos potenciais zeta obtidos (+14,1 mV a +44,8 mV), demonstram que os agregados são estáveis em solução, característica fundamental para aplicação no transporte de fármacos. A capacidade de encapsulamento do fármaco quercetina por esses derivados foi avaliada por estudos de incorporação utilizando a espectroscopia UV-Vis. Os resultados obtidos demonstraram que o comportamento dos derivados depende de parâmetros como o grau de hidrofilicidade e grupo hidrofílico, grau de hidrofobicidade e pH do meio de encapsulamento, possibilitando controlar a quantidade de fármaco contida nos carreadores. A atividade biológica dos agregados formados pelos derivados de quitosana foi testada em células de adenocarcinoma de mama (MCF-7) e os resultados indicaram baixa toxicidade dos carreadores, além de potencialização do efeito terapêutico do fármaco. Estudos de microscopia confocal de varredura a laser evidenciaram que agregados marcados com proteína verde fluorescente com afinidade por quitosana (CAP-sfGFP) foram internalizados pelas células MCF-7. Resultados de hemocompatibilidade indicaram que os polímeros apresentam baixa destruição de glóbulos vermelhos do sangue e liberação de hemoglobina. Portanto, esses derivados possuem características adequadas para aplicação no transporte e liberação controlada de fármacos.This thesis presents results of structural modifications, characterizations and applications of chitosan derivatives as drug carriers. Amphiphilic derivatives of chitosan containing hydrophilic and hydrophobic groups were characterized by nuclear magnetic resonance spectroscopy (RMN1H), infrared spectroscopy (IV), uv-vis spectroscopy, thermoanalytical techniques (thermogravimetry (TGA), derivative thermogravimetry (DTG), differential thermal analysis (DTA) and differential exploratory calorimetry (DSC)), fluorescence, dynamic light scattering (DLS) and transmission electron microscopy (MET). The characterization results showed that the proposed syntheses were successfully performed. The critical aggregation concentration (CAC), DLS and MET studies confirmed that the derivatives self-assembled in aqueous solution forming aggregates with diameters ranging from 230 to 500 nm. These values, associated with zeta potentials (+14.1 mV to +44.8 mV), demonstrate that the aggregates were stable in solution. The ability to encapsulate quercetin by these derivatives was assessed by incorporation studies using UV-Vis spectroscopy. The results showed that the behavior of the derivatives depends on parameters such as the degree of hydrophilicity and hydrophilic groups, degree of hydrophobicity and pH of the encapsulation medium. The biological activity of the aggregates formed by the chitosan derivatives was tested in breast cancer cells (MCF-7) and the results indicated low toxicity of the carriers, in addition to improving the therapeutic effect of the drug. Confocal laser scanning microscopy studies showed that aggregates stained with chitosan-affinity protein (CAP-sfGFP) were internalized by MCF-7 cells. Hemolysis assays showed good hemocompatibility of chitosan derivatives. Therefore, the derivatives have suitable characteristics for application as drug delivery systems.
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Isaacs, Rabia. "The in vitro effects of nicotine and selected antibiotics, tunicamycin and thapsigargin on human Breast carcinoma (mcf-7) cells." University of the Western Cape, 2012. http://hdl.handle.net/11394/4579.
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>Magister Scientiae - MScCancer is defined as the abnormal growth of genetically mutated or perturbant cells. Nicotine is a known cancer promoter and an apoptotic suppressor. This alkaloid acts on the nicotinic acetylcholine receptors which affects the ubiquitin-proteasome protein degradation pathway and ultimately hinders apoptosis. The endoplasmic reticulum (ER) is an interconnecting organelle which synthesises proteins and its quality control processes ensures the proper protein folding, post-translational modifications and conformation of secretory and trans-membrane proteins. Studies demonstrated that the antibiotic, Tunicamycin (Tm) and the sesquiterpene lactone, Thapsigargin (Tg) causes ER stress and consequently cellular arrest. Tm interferes with N-glycosylation of newly synthesised proteins triggering the unfolded protein response, while Tg inhibits intracellular Ca2+ ATPases resulting in increased cytosolic Ca2+. Studies showed that these compounds have potential pro-apoptotic effects. The combinatorial effects of nicotine, Tm and Tg may produce antagonistic or synergistic effects and provide a therapeutic tool against breast cancer. The aim of the study was to determine the apoptotic effects of nicotine, Tm, and Tg on human breast carcinoma (MCF-7) at various time intervals and further to elucidate whether selected ratios of their combinations resulted in synergistic or antagonistic effects.
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Kushwaha, Neena. "Mechanisms of 17-beta-estradiol regulation of the proto-oncogene Bcl-2 in MCF-7 human breast cancer cells." Thesis, University of Ottawa (Canada), 2002. http://hdl.handle.net/10393/6361.
Full textAbstract:
In the present studies, the mechanisms of estrogen regulation of Bcl-2 were investigated by analyzing the expression of different Bcl-2 promoter-driven constructs stably transfected into MCF-7 cells. An approximately 1.7 kilobase (kb) sequence which directed estrogen-dependent regulation of Bcl-2 expression in these stable MCF-7 clones was identified. Another agent which may play a role in the regulation of Bcl-2 expression is the tumour suppressor gene, p53. We investigated the effects of various mutant p53 proteins and low levels of p53 on Bcl-2 expression in MCF-7 cells. Neither MCF-7/E6 cells expressing virtually undetectable levels of p53 nor MCF-7/173L cells expressing a DNA binding domain mutant p53, showed altered E2-mediated induction of Bcl-2 mRNA or protein levels. However, MCF-7 cells expressing a truncated mutant p53 protein (Delta291) resulted in a dramatic decrease in Bcl-2 protein levels, but not mRNA levels, upon E2 treatment. These results suggest that a p53 protein lacking a carboxy-terminus may cooperate with E2 post-transcriptionally to negatively regulate Bcl-2 levels in MCF-7 human breast cancer cells. (Abstract shortened by UMI.)
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Stuart, Andrew. "The role of P450RAI in an autoregulatory feedback loop mechanism involved in regulating RA level in MCF-7 and NB4 cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0002/MQ59405.pdf.
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Chen, Chiau-Yi, and 陳喬依. "Specific Targeting of MCF-7 Breast Cancer Stem Cells." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/87647653272361497951.
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碩士高雄醫學大學
天然藥物研究所
100
Stem cell plays important roles in the physiological functions of normal human. It is believed that cancer stem cell also contribute heavily to tumor formation. Cancer stem cells can also be found in established cancer cell lines, albeit in low frequency. It’s capable of self-renewal, continuous division and differentiation, thereby promote cancer proliferation. Therefore current research tends to focus on finding therapeutic agents that can eliminate cancer stem cells. In this study we tested the effect of 5-azacytidine, a DNA methyltransferase inhibitor (DNMTI). Cancer stem cells were grown in serum-free culture conditions as tumorspheres. Cytotoxicity of 5-azacytidine in MCF-7 human breast cancer stem cells survival rate was determined by MTT assay. IC50 of this drug to be approximately 10 μΜ. Cancer stem cells display a very high degree of resistance to chemotherapy and radiotherapy. This study suggests that 5-azacytidine has therapeutic potential treating in human breast cancer cell in MCF-7 by selectively targeting cancer stem cells and may provide a more effective therapeutic strategy. 5-azacytidine at this concentration significantly inhibited MCF-7 mammosphere formation, wound healing ability and MMP-9 production. Western blotting indicated 5-azacytidine induced cleavage of caspase-7 and PARP indicative of apoptosis.
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Mannon, Sara. "Effects of endosulfan on human MCF-7 breast cancer cells." Thesis, 2011. http://hdl.handle.net/10155/193.
Full textAbstract:
Organochlorine pesticides (OCs) are environmental toxicants with important links to human health. They have been found to activate signalling pathways within cells and thereby affect cell survival and proliferation. Receptor Activator of Nuclear Factor kB (RANK) ligand and its receptor RANK are crucial for mammary epithelial proliferation in pregnancy and have recently been linked to hormone induced breast cancers. The objectives of this study were to confirm the proliferative effects of an OC (endosulfan) on human MCF-7 breast cancer cells, identify activated intracellular signaling pathways and investigate changes in RANK and RANKL gene expression. This study showed that endosulfan has a stimulatory effect on human MCF-7 cell proliferation, which may be invoked through activated intracellular signaling pathways (JNK, ERK1/2 and p38). In addition, there was a down regulation of RANK and upregulation of RANKL gene expression suggesting endosulfan is capable of modulating both cellular behavior and gene expression.UOIT
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Lin, Yeh-Ssu, and 林曄思. "The Effect of Tryptanthrin in MCF-7 Breast Cancer Cells." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/08668569688413462113.
Full textAbstract:
碩士國立臺灣大學
藥學研究所
97
Multidrug resistance (MDR), the resistance of tumor cells to anticancer agents, remains a major cause of treatment failure for cancer patients. MDR usually occurs with alteration of function and expression of some proteins and enzymes, for example P-gp (P-glycoprotein), MRP (multidrug resistance-related protein), topoisomerase and glutathione. Recently, the genes which show differential expressions in MCF-7/WT and its doxorubicin-resistant counterpart MCF-7/ADR include ER-α (estrogen receptor α), ER-β (estrogen receptor β), PR (progesterone receptor), VEGF（vascular endothelial growth factor）, HIF-1α ( hypoxia-inducible factor-1α ) , FoxO1（forkhead box-containing protein，O subfamily）, C/EBP β（CCAAT/enhancer-binding protein β）, CtBP1(C-terminal binding protein 1), dicer 1, argonaute 2, PIM-1 and PKc α (protein kinase c α). Our lab previously demonstrated that tryptanthrin could reverse the resistance to doxorubicin in MCF-7/ADR. In order to extensively understand the mechanisms of multidrug resistance, MCF-7/WT and MCF-7/ADR were treated with trptanthrin to examine the changes in expression of the above genes in this study, using RT-PCR, realtime-PCR and Western blot. Results show that tryptanthrin suppresses the expression of nuclear receptor genes in MCF-7/WT. The expression of ER-α is 50％ down. Furthermore, the binding of SP1 family proteins to ER-α promoter site IEF-1 decreases upon tryptanthrin treatment. In mRNA level, tryptanthrin inhibits the expression of PR prior to the expression of ER-α. As PR is downstream protein of ER-α, it seems that tryptanthrin acts on PR and ER-α via different pathways. When ER-α expression was knockdowned by siRNA in MCF-7/WT, the expression of MDR1 gene did not induced, suggesting the decrease in ER-α was not related to MDR1 gene expression in MCF-7/ADR.
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Chong, Meng-Chin, and 鍾孟芹. "Effects of synthetic peptide and black soybean on MCF-7 cells." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/01672618993745944906.
Full textAbstract:
碩士中國醫藥大學
營養研究所
92
In recent years, several kinds of western medicines for the breast cancer therapy were reported to have many side effects. Therefore, the herbal medicine and food become popular topics in studies related to the development of anticancer agents. Some studies indicated that those who intake more soybean products have the lower morbidity of breast cancer and prostate cancer. The objective of this study is to evaluate effects of the black soybean and the synthetic peptide on breast cancer cells. Water extract of Tainan No.5 black soybean (black soybean milk, T5) was freeze-dried. ER+ MCF7 cells were treated with various concentrations of T5 (0, 0.15, 0.31, 0.62, 1.25, 2.50 mg/mL) for various times and then analyzed for their effects on cell viability and cell cycle distribution by flow cytometry. Following treatment with 2.50 mg/mL T5 for 12, 24, 48, and 72 hrs, cell viability decreased to 47%, 26%, 10%, 6%, respectively, compared with control group (100 %). S-phase arrest was found in ER+ MCF7 cells treated with 2.5 mg/mL T5 for 24 hrs. The proportions of apoptotic cells were significantly increased in ER+ MCF7 cells treated with 2.5 mg/mL T5 for 48 and 72hrs. These results suggest that effects of T5 on ER+ MCF7 breast cancer cells were related to its inhibition on the cell cycle progression. The inhibitory effects of synthetic peptides on the Grb2 SH2 interaction were evaluated by SPR, and Fmoc-Glu-Tyr-Aib-Asn-NH2 (peptide 3) was found to be the lead compound with the highest inhibitory effect. For further evaluate its effect on breast cancer cells, ER+ MCF7 cells were treated with various concentrations of the peptide 3 (0, 12.5, 25.0, 37.5, 50.0, 62.5 μM) for various times and then analyzed for their effects on cell viability and cell cycle distribution by flow cytometry. S-phase down-regulated was found in ER+ MCF7 cells treated with 12.5 μM of peptide 3 for 24 hrs. The proportions of apoptotic cells were significantly increased to 8% and 17% in ER+ MCF7 cells treated with 50.0 μM and 62.5 μM of peptide 3 for 24 hrs. Results of this study indicate that black soybean and the small molecular weight peptide, Fmoc-Glu-Tyr-Aib-Asn- NH2, have biological effects on breast cancer cells.
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TSAI, CHONG-BIN, and 蔡忠斌. "Fenofibrate Induces Lipogenesis and Paraptosis of MCF-7 Breast Cancer Cells." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/gm6a2p.
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博士國立中正大學
生命科學系分子生物研究所
105
Breast cancer is the most common invasive cancer in women worldwide. Conventional breast cancer therapies include surgical resection, radiotherapy, and chemotherapy. Despite the recent development of adjuvant therapies targeting estrogen and growth factor pathways, the incidence of breast cancer has not declined. Therefore, the search for new therapeutic targets and treatment modalities are necessary. One of the strategies of effective cancer therapy is induction of cell death of cancer cells using various cytotoxic agents. Apoptosis is the most well-known modality of cell death. In 2000, Sperandio et al. described a form of programmed cell death called paraptosis, which is morphologically and biochemically distinct from apoptosis. Paraptosis was associated with extensive cytoplasmic vacuolization and mitochondrial swelling, but without any other morphological hallmark of apoptosis. The other important strategy of cancer therapy, Pierce introduced the concept of differentiation therapy that malignant cells can differentiate into non-malignant cells in 1971. The development of differentiation therapy required the identification of targetable pathways to re-activate blocked terminal differentiation programs in cancer cell. Recent studies showed that enhanced expression of PPARs in malignant tissue implicates the possible involvement of PPARs signal pathway in tumorigenesis. It also has been shown that PPARs are involved in cell differentiation programs during development. However, published evidences were mainly on the work of PPARγ. In this research, we focused the fate of MCF7 breast cancer cell after treating with PPARα agonist fenofibrate. The potential anti-proliferative actions of fenofibrate on MCF7 cells were studied through the analyses of inhibition of cell viability, cell cycle analysis, cloning-forming capacity and appearance of cell paraptosis. The differentiation-inducing abilities of fenofibrate were studied through induction of mammary glandular characteristics, including lipid accumulation and casein expression. DNA Microarray analysis was also applied to elucidate the up- and down-regulatory genes affect by fenofibrate treatment. Analyses of differential expressed genes by Ingenuity Pathway Analysis and STRING Database implied the potential ability of fenofibrate to alter cell fate of breast cancer cell was via inhibition of cell cycle and activation of ER stress pathway, esp. PERK pathway. This study outlined the signaling pathway of fenofibrate-induced differentiation and paraptosis of MCF-7 cells. Fenofibrate activated PERK of ER stress, and increased the expression levels of downstream cascade genes, ATF4, ATF3, CHOP and TRB3. TRB3 could inhibit PI3K/Akt cell survival signal to decrease cell viability. In addition, ATF3 associated with p53 to stabilize it, stabilized p53 stimulated p21 expression. Increased p53 and p21 suppressed expression of cyclin D1, CDK4 and CDK6 and ATF3 could also inhibit expression of cyclin D1. Eventually entry of cells into cell cycle S phase was prevented and arrested cells in cell cycle G1/Go phase. The cell cycle arrest might initiate the process of mammary glandular differentiation of MCF-7 cells. On the other hand, TRB3 could also activate MAPK pathway which has been shown to mediate paraptosis.
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Peres, Carina Sofia Gonçalves. "Androgens in breast cancer cells physiology: a connection with calcium homeostasis?" Master's thesis, 2012. http://hdl.handle.net/10400.6/2871.
Full textAbstract:
Several evidences suggest that androgenic actions and calcium (Ca2+) homeostasis alterations may contribute to the development of breast cancer. The androgen receptor is detected in the majority of human breast cancer cases, including those that are oestrogen and progesterone receptor negatives. It has also been shown that androgens play an important role regulating breast cells proliferation and death. On the other hand, it is known that intracellular Ca2+ is a ubiquitous second messenger involved in the regulation of several biological processes in the cell such as proliferation and apoptosis. In this way, deregulation of intracellular Ca2+ concentration via altered expression and/or function of Ca2+ transporters, Ca2+ channels and/or Ca2+ binding proteins may have implications breast pathophysiology. Recently, studies have demonstrated that androgens regulate the expression and/or activity of several Ca2+ regulator proteins, namely the Ca2+-binding protein regucalcin and voltage-dependent L-type Ca2+ channel in distinct cell types. The present project aims to investigate the effect of androgen 5α-dihydrotestosterone (DHT) on the expression of regucalcin and L-type Ca2+ channel (α1C subunit) in human breast cancer cells (MCF-7). The presence of regucalcin and L-type Ca2+ channel (α1C subunit) in these cells was confirmed by means of RT-PCR and Western Blot. The effect of androgens on the mRNA expression of regucalcin and L-type Ca2+ channel (α1C subunit) was evaluated by real-time PCR. DHT down-regulated the expression of regucalcin and L-type Ca2+ channel (α1C subunit) in MCF-7 cells. In both cases, this effect was reverted in presence of androgen inhibitor flutamide and oestrogen inhibitor ICI 182,780, suggesting that DHT effects regulating regucalcin and L-type Ca2+ channel (α1C subunit) expression are mediated by the androgen receptor, but also by the oestrogen receptor due to the metabolization of DHT to oestrogenic products. This study first demonstrated the presence of L-type Ca2+ channel (α1C subunit) in human breast cancer cells and showed that androgens modulate expression of Ca2+ regulator proteins in these cells. These findings suggest that androgenic actions regulating cell death and proliferation of breast cancer cells may be associated with the control of Ca2+ homeostasis.Várias evidências sugerem que as ações androgénicas e alterações na homeostasia do cálcio (Ca2+) podem contribuir para o desenvolvimento do cancro de mama. O recetor de androgénios é detetado na maioria dos casos de cancro de mama humano, incluindo os que são considerados negativos para os recetores de estrogénios e de progesterona. Também se tem demonstrado que os androgénios desempenham um papel importante na regulação da proliferação e morte em células da mama. Por outro lado, sabe-se que o Ca2+ intracelular é um segundo mensageiro ubíquo envolvido na regulação de diversos processos biológicos da célula, tais como a proliferação e a apoptose. Desta forma, a desregulação da concentração intracelular de Ca2+ , através de alterações na expressão e/ou função de transportadores de Ca2+, canais de Ca2+ e/ou proteínas de ligação ao Ca2+ , pode ter implicações na fisiopatologia da mama. Recentemente, alguns estudos demonstraram que os androgénios regulam a expressão e/ou atividade de várias proteínas reguladoras de Ca2+, nomeadamente a proteína de ligação ao Ca2+ regucalcina e o canal de Ca2+ dependente de voltagem do tipo L, em tipos celulares distintos. Com o presente projeto pretende-se investigar o efeito do androgénio 5αdihidrotestosterona (DHT) na expressão da regucalcina e do canal de Ca2+ do tipo L (subunidade α1C) em células de cancro da mama humano (MCF-7). A presença da regucalcina e do canal de Ca2+ do tipo L (subunidade α1C) nestas células foi confirmada por RT-PCR e Western Blot. O efeito dos androgénios na expressão do mRNA da regucalcina e do canal de Ca2+ do tipo L (subunidade α1C) foi avaliado por PCR em tempo real. A DHT diminui a expressão da regucalcina e do canal de Ca 2+ do tipo L (subunidade α1C) em células MCF-7. Em ambos os casos, este efeito foi revertido em presença do inibidor de androgénio flutamida e do inibidor de estrogénios ICI 182,780, sugerindo que os efeitos da DHT na regulação da expressão da regucalcina e do canal de Ca2+ do tipo L (subunidade α1C) são mediados pelo recetor de androgénios, mas também pelo recetor de estrogénios devido à metabolização da DHT em produtos estrogénicos. Este estudo demonstrou primeiramente a presença do canal de Ca2+ do tipo L (subunidade α1C) nas células de cancro da mama humano e demonstrou que os androgénios regulam a expressão de proteínas reguladoras de Ca2+ nestas células. Estes resultados sugerem que a ação reguladora dos androgénios na proliferação e morte celular nas células de cancro da mama pode estar associada ao controlo da homeostasia do Ca2+ .
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Lee, Pei-Jing, and 李佩菁. "Effect of Hypoxia on Glucose Transport in MCF-7 Breast Tumor Cells." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/85319464726833274371.
Full textAbstract:
碩士國立陽明大學
生物化學研究所
91
In cancer cells, the blood flow is decreased when solid tumor forms. In order to survive in this hypoxic condition, the cells use anaerobic glycolysis to produce more energy. Many enzymes and proteins involved in glycolysis are known to be up-regulated under hypoxia, including glucose transporter 1. We used cobalt chloride and sodium azide to mimic two different pathways that may be activated by hypoxia, and 95% N2 plus 5% CO2 to induce hypoxic condition. All these three treatments induce 2-DG uptake in MCF-7 breast cancer cells. We transfected luciferase reporter vector driven by glut1 promoter into MCF-7 cells, and found that cobalt chloride and hypoxia but sodium azide induced the transcriptional activity. Both PI3 kinase and calmodulin seems to be involved in the effect of cobalt chloride, whereas only PI3 kinase is involved in the effect of hypoxia. In addition, only cobalt chloride can induce the formation of interacellular reactive oxygen species (ROS) in a calmodulin-dependent manner. Western blot was used to analysis the protein level of HIF-1α. Cobalt chloride and hypoxia but not sodium azide can increase the protein level of HIF-1α. An inhibitor of PI3 kinase, wortmannin, can decrease the quantity of HIF-1α induced by cobalt chloride and hypoxia. However wortmannin can only suppress the 2-DG uptake induced by hypoxia, but not that induced by cobalt chloride. Thus it suggests that cobalt chloride and hypoxia may induced 2-DG uptake in MCF-7 breast tumor cells through different pathways. Sodium azide has no effect on glut1 gene expression, although it can stimulate 2-DG uptake. We suggest that sodium azide may exert its influence by a post-translational mechanism, and both p38 MAPK and PKC may be involved in this effect. Taken together, we suggest that the induction of glucose transport by these three different treatments may be mediated by different pathways.
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Tseng, Jen-chih, and 曾仁志. "p53 tumor suppressor protein is associated with metastasis in MCF-7 cells." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/97714685583276385614.
Full textAbstract:
碩士東吳大學
微生物學系
95
Breast cancer in woman was the highest mortality rate, despite advance in clinical therapy in treating breast cancer. p53 is a tumor suppression protein and has been mutated in many cancers, including the breast cancer. It has been found that estrogen receptor-α which is one of the target for therapy is an important growth regulation for breast cancer cells. P53 and ER-α are often lost in the process of breast cancer development, especially in advanced breast cancers which are more invasive and metastatic than the early-stage breast cancers. In this theses, the involvement of p53 and ER-α in the breast cancer metastasis was analyzed. The results showed that dominant negative p53 and p53 siRNA increased the degree of metastasis as determined by suspension survival assay and cell attachment assay. The cell cycle progression was also accelated especially at G2/M stage. On the other hand the addition of E2 decreased the MCF-7 metastasis, and such effect was blocked by antiestrogen ICI 182,780. The MCF-7 and MDA-MB-231 membrane adhesion molecule profile was companed to explain the difference of adhesion property. The flow cytometry analysis showed the p53 knock down resulted in the increase of integrin αv slightly. In the future, the questions of how p53 and ER-α regulate the breast cancer metastasis will be worth to further exposured.
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Mei-yinLin and 林美吟. "Proteomics Study of Estrogen Agonist-Induced Transcriptional Complex in MCF-7 cells." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/41699580585052772453.
Full text
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"Growth inhibitory effects of chlorophyllin on human breast carcinoma MCF-7 cells." 2005. http://library.cuhk.edu.hk/record=b5892491.
Full textAbstract:
Kong Ka-lai.Thesis (M.Phil.)--Chinese University of Hong Kong, 2005.
Includes bibliographical references (leaves 126-149).
Abstracts in English and Chinese.
Acknowledgements --- p.i
Abstract --- p.ii
Abstract (Chinese Version) --- p.vi
Table of Contents --- p.ix
List of Figures/Table --- p.xiii
List of Abbreviations --- p.xvi
Chapter Chapter 1 --- General Introduction
Chapter 1.1 --- An Overview on Cancer --- p.1
Chapter 1.2 --- Biological Effects of Chlorophyllin --- p.7
Chapter 1.2.1 --- CHL as Photosensitizer --- p.7
Chapter 1.2.2 --- CHL as Antioxidant --- p.8
Chapter 1.2.3 --- CHL as Anticarcinogenic Agent --- p.9
Chapter 1.3 --- Regulation of Cell Cycle --- p.13
Chapter 1.3.1 --- Cell-Cycle Checkpoints --- p.13
Chapter 1.3.2 --- Cell-Cycle Regulatory Proteins --- p.15
Chapter 1.4 --- Regulation of Mitogen-Activated Protein Kinase (MAPK) Signaling Cascade --- p.21
Chapter 1.5 --- Programmed Cell Death (or Apoptosis) --- p.27
Chapter 1.5.1 --- Regulation of Caspase-Dependent Apoptosis --- p.28
Chapter 1.5.2 --- Regulation of Caspase-Independent Cell Death --- p.32
Chapter 1.5.3 --- Bcl-2 Family Proteins in Modulation of Cell Death --- p.32
Chapter 1.6 --- In Vivo Antitumor Screening System --- p.37
Chapter 1.7 --- Aims of the Present Study --- p.38
Chapter Chapter 2 --- In Vitro Studies of the Anticancer Effect of Chlorophyllin
Chapter 2.1 --- Introduction --- p.39
Chapter 2.1.1 --- DNA-Flow Cytometric Analysis --- p.51
Chapter 2.1.2 --- Western Blot Analysis --- p.54
Chapter 2.2 --- Materials and Methods --- p.56
Chapter 2.2.1 --- Maintenance of Cell Lines --- p.56
Chapter 2.2.2 --- Cytotoxic and Cytostatic Effects on the Cancer Cells --- p.56
Chapter 2.2.3 --- DNA-Flow Cytometric Analysis --- p.60
Chapter 2.2.4 --- Western Blot Analysis --- p.61
Chapter 2.2.5 --- JC-1 Mitochondrial Potential Sensor --- p.64
Chapter 2.2.6 --- Caspase Inhibitors --- p.65
Chapter 2.2.7 --- Statistical Analysis --- p.66
Chapter 2.2.8 --- Densitometric Analysis --- p.66
Chapter 2.3 --- Results --- p.67
Chapter 2.3.1 --- Effects of CHL on the Growth of Human Cancer Cells by MTT Assay --- p.67
Chapter 2.3.2 --- Effect of CHL on the Proliferation of MCF-7 Cells by Chemi-BrdU Incorporation --- p.69
Chapter 2.3.3 --- Effect of CHL on Cell Cycle of MCF-7 Cells --- p.71
Chapter 2.3.4 --- Effect of CHL on the Cyclin D1 Expression in MCF-7 Cells --- p.74
Chapter 2.3.5 --- Effects of CHL on JNK and c-Jun Expressions and Their Phosphorylations in MCF-7 Cells --- p.76
Chapter 2.3.6 --- Effect of CHL on DNA fragmentation in MCF-7 Cells --- p.78
Chapter 2.3.7 --- Effect of CHL on Mitochondrial Membrane Potential of MCF-7 Cells --- p.80
Chapter 2.3.8 --- Effects of CHL on the PARP Expression and Cleavage in MCF-7 Cells --- p.83
Chapter 2.3.9 --- "Effects of CHL on Bcl-2, Bcl-xL and Bad Expressions in MCF-7 Cells" --- p.85
Chapter 2.3.10 --- Effects of CHL on Caspase Activations in MCF-7 Cells --- p.88
Chapter 2.3.11 --- Effects of Caspase Inhibitors on the CHL-Induced Apoptosis in MCF-7 Cells --- p.90
Chapter 2.4 --- Discussion --- p.93
Chapter Chapter 3 --- In Vivo Studies of the Anticancer Effect of Chlorophyllin
Chapter 3.1 --- Introduction --- p.104
Chapter 3.2 --- Materials and Methods --- p.106
Chapter 3.2.1 --- Transplantation of MCF-7 Cells into the Nude Mice and Treatment --- p.106
Chapter 3.2.2 --- Western Blot Analysis --- p.107
Chapter 3.2.3 --- Statistical Analysis --- p.107
Chapter 3.3 --- Results --- p.108
Chapter 3.3.1 --- In Vivo Antitumor Activity of CHL --- p.108
Chapter 3.3.2 --- In Vivo Effects of CHL on Cyclin D1 and Bcl-2 Expressions in MCF-7 Solid Tumor --- p.111
Chapter 3.4 --- Discussion --- p.113
Chapter Chapter 4 --- General Discussion --- p.115
References --- p.126
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Chou, Yu-Hsuan, and 周毓軒. "Med28 (Magicin) Regulates Migration and Cell Cycle Progression in MCF-7 Human Breast Cancer Cells." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/37915155680884843493.
Full textAbstract:
碩士中國醫藥大學
營養學系碩士班
99
Magicin (Med28) exhibits multiple cellular roles. The interaction of Med28 with Grb2, Src, merlin, and actin cytoskeleton, strongly suggests that Med28 involves in many cellular signaling pathways. Several tumors overexpress Med28, whereas the role of Med28 in tumor development is unclear. The objective of this study is to understand the role of Med28 in cellular migration and proliferation using Med28 over-expressing MCF-7 breast cancer cells as a model. RNA interference-mediated depletion of Med28 inhibited cellular migration and matrix metalloproteinase-2 (MMP-2) activation in MCF-7 cells. In addition, Med28 siRNA delayed cell cycle progression, decreased cyclin D1 expression, and increased HMG-box transcription factor 1 (HBP1) expression. The disruption of Med28 also inhibited the expression of several migration-related signaling molecules, including MEK1. In Med28-overexpressing cells, RNA interference-mediated depletion of MEK-1 inhibited migration with a respectively decreasing matrix metalloproteinase-2 (MMP-2) activation. These data suggest that Med28 might regulate MMP-2-mediated cellular migration via MEK1/ERK signaling pathway. Taken together, our data demonstrate that Med28 involves in cellular migration and proliferation in breast cancer cells, which may have clinical application in the intervention of breast cancer.
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Wang, Yu-Fen, and 王毓芬. "The Mechanism of Capsaicin-induced Apoptosis in Human Breast Cancer MCF-7 Cells." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/98191939722017229571.
Full textAbstract:
碩士國立彰化師範大學
生物技術研究所
95
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a major pungent ingredient in a variety of red peppers of the genus Capsicum, is a type of vanilloids. It has been shown to exert biological activities (anticarcinogenic, antimutagenic and chemopreventive activities) in many cancer cell lines. It was found that capsaicin induces dose-dependent growth inhibition of MCF-7 cells, which do not express caspase-3. In this study, we investigated the molecular mechanism of capsaicin-induced apoptosis in MCF-7 cells. Treatment with capsaicin for 24 hours resulted in a dose-dependent apoptosis in MCF-7 cells. After addition of capsaicin, levels of reactive oxygen species (ROS) reduced slightly in the earlier time of treatment. Interestingly, an elevation of intracellular calcium ion (Ca2+) concentration was also detected in MCF-7 cells. In time course and dosage studies, mitochondrial membrane potential of MCF-7 cells decreased. Nonetheless, the change was not significant. It is worth noting that apoptosis-inducing factor (AIF) translocated into the cytosol and nucleus from mitochondria. Our results suggest that capsaicin may induce cellular apoptosis through caspase-independent pathway in MCF-7 cells, and that ROS and intracellular Ca2+ fluctuation may have a minimal role in the process.
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Fan, Ya-Chun, and 范雅鈞. "Clozapine induces autophagy and apoptosis in MCF-7 cells through reactive oxygen species." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/65814038475786564335.
Full textAbstract:
碩士國立臺灣海洋大學
生物科技研究所
101
Even though recent studies demonstrated antipsychotics have antiproliferative activity in cancer cell lines, the mechanisms are not fully elucidated. Clozapine has inhibitory effect on cell growth in MCF-7 cells by MTT and clonogenic assay. Flow cytometric analysis exhibited that the exposure of MCF-7 cells to clozapine led to the G0/G1 phase arrest by decreasing CyclinD1, CDK4, CDK6 and increasing CDK inhibitor p21 and p27 protein levels. Exposure of MCF-7 cells to increasing dosage of clozapine during 72 h significantly increased the production of reactive oxygen species (ROS), apoptosis and autophagy. A ROS scavenger vitamin E reduced ROS, apoptosis and autophagy, then recoveried cell survival. Blocking autophagy by chloroquine could increase clozapine-induced ROS and promoteclozapine-induced apoptosis. Our study proved for the first time that clozapine inhibited MCF-7 cell growth by inducing G0/G1 cell cycle arrest, apoptosis and autophagy via a ROS dependent manner. Clozapine-induced autophagy decreased ROS to protect cancer cell from apoptosis. These data suggested that combined clozapine and autophagy inhibitor will effectively kill MCF-7 cancer cells.
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Hieu, Bui Thi Ngoc, and 裴氏玉孝. "Antitumor Effects of Wikstroemia indica Extracts on Human Breast Cancer MCF-7 Cells." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/57183617609394505135.
Full textAbstract:
碩士中國文化大學
生物科技研究所
103
Wikstroemia indica has been demonstrated as a plant that contains the most abundant bioactivity components for treating many diseases as syphilis, arthritis, whooping cough, and cancer. Cell culture methods can be applied to amplify MCF-7 cell populations and detect the antitumor effects of W. indica extracts. We assess 3 differently extractive criteria of W. indica compounds via cell-proliferation (MTT), cell-migration, cell cycle, apoptosis and real-time – reverse transcriptase – polymerase chain reaction (real-time RT-PCR) assays. Initially, we determined its anticancer potential at increasingly serial concentrations from 8.125 to 130 µg/ml of the W. indica extracts with 4 different time frames. W. indica extracts remarkably inhibited cell proliferation result at highest concentrations of 3 samples (Sample A, B, C) after 6 hours hence constantly lasting inhibition ability for 24 hours. Secondly, migration results have similar effect with the same concentration (130 µg/ml) after 12h. Thirdly, cell cycle result as we expected that W. indica extracts to trap major of MCF-7 cells in Sub-G1 phase. Due to sub-G1 phase ambushed cells related to cell death program via apoptosis assay. The real-time RT-PCR results could convince the previous experiments to discover the intracellular apoptotic mechanism. Hopefully, these significant results could improve evidences for useful anticancer agents hence approach in breast cancer treatments.
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Fuelling, Allison Jean. "Induction of apoptosis upon overexpression of phosphatidylinositol phosphate kinases in MCF 7 cells." 2000. http://catalog.hathitrust.org/api/volumes/oclc/45549451.html.
Full textAbstract:
Thesis (M.S.)--University of Wisconsin--Madison, 2000.Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 59-64).
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"Flavonoids display differential actions on er transactivation and apoptosis in MCF-7 cells." 2002. http://library.cuhk.edu.hk/record=b5896009.
Full textAbstract:
Po Lai See.Thesis (M.Phil.)--Chinese University of Hong Kong, 2002.
Includes bibliographical references (leaves 142-152).
Abstracts in English and Chinese.
TITLE PAGE --- p.p.1
ACKNOWLEGDEMENTS --- p.p.2
ABSTRACT --- p.p.3
摘要 --- p.p.6
TABLE OF CONTENTS --- p.p.9
LIST OF FIGURES AND TABLES --- p.p.16
Chapter CHAPTER 1 --- GENERAL INTRODUCTION
Chapter 1.1 --- Estrogen and Estrogen Receptors and its Action --- p.p.18
Chapter 1.1.1 --- Estrogen --- p.p.19
Chapter 1.1.2 --- Estrogen Receptors --- p.p.19
Chapter 1.1.3 --- Structural Differences between ERa and ERp --- p.p.21
Chapter 1.1.4 --- Functional Differences --- p.p.22
Chapter 1.1.5 --- Effects of Selective Estrogen Receptor Modulators --- p.p.22
Chapter 1.1.6 --- Estrogen works --- p.p.23
Chapter 1.1.7 --- Estrogen Receptors and Breast Cancer --- p.p.24
Chapter 1.2 --- Flavonoids： Properties and Biological Activities --- p.p.25
Chapter 1.2.1 --- Chemical Structure and Classification of flavonoids --- p.p.25
Chapter 1.2.2 --- Biological Properties and Action Mechanism of Flavonoids… --- p.p.27
Chapter 1.2.3 --- Flavonoids and breast cancer prevention --- p.p.27
Chapter 1.3 --- Aims and Scopes of Investigation --- p.p.29
Chapter CHAPTER 2 --- MATERIALS AND METHODS
Chapter 2.1 --- Chemicals --- p.p.30
Chapter 2.1.1 --- Flavonoids --- p.p.30
Chapter 2.1.2 --- Plasmids --- p.p.30
Chapter 2.2 --- Mammalian cell culture --- p.p.31
Chapter 2.2.1 --- Maintenance of cells --- p.p.31
Chapter 2.2.2 --- Preparation of cell stock --- p.p.32
Chapter 2.2.3 --- Cell recovery from liquid nitrogen stock --- p.p.32
Chapter 2.3 --- Identification of estrogenic activity in flavonoids --- p.p.33
Chapter 2.3.1 --- Steady Glo Luciferase Assay --- p.p.33
Chapter 2.3.2 --- The Biorad Protein Assay kit (a modified Bradford method). --- p.p.33
Chapter 2.4 --- Viability Assay --- p.p.34
Chapter 2.5 --- ERE Luciferase reporter gene assay --- p.p.35
Chapter 2.5.1 --- Transient transfect ion of cell using lipofectamine PLUS reagent --- p.p.36
Chapter 2.5.2 --- Dual Luciferase Assay --- p.p.37
Chapter 2.6 --- ERα competitive binding ASSAY --- p.p.37
Chapter 2.7 --- Apoptotic death assay --- p.p.38
Chapter 2.8 --- Semi-quantitative RT-PCR Assay --- p.p.40
Chapter 2.8.1 --- "Isolation of RNA using TRIzol® Reagent (Life Technology,USA) " --- p.p.40
Chapter 2.8.2 --- Quantitation of RNA --- p.p.41
Chapter 2.8.3 --- First strand cDNA synthesis --- p.p.41
Chapter 2.8.4 --- PCR reactions --- p.p.43
Chapter 2.9 --- Flow Cytometry Analysis --- p.p.43
Chapter 2.10 --- Total triglyceride and cholesterol measurement --- p.p.44
Chapter 2.10.1 --- Determination of the total cholesterol --- p.p.45
Chapter 2.10.2 --- Determination of the total triglyceride --- p.p.46
Chapter 2.11 --- Manipulation of DNA and RNA --- p.p.46
Chapter 2.11.1 --- Transformation of DH5α --- p.p.46
Chapter 2.11.2 --- Mini preparation of plasmid DNA --- p.p.47
Chapter 2.11.3 --- Preparation of plasmid DNA using QIAGEN-tip 100 midi-prep kit --- p.p.48
Chapter 2.11.4 --- Preparation of plasmid DNA using QIAGEN-tip 10000 Giga-prep kit --- p.p.49
Chapter 2.11.5 --- Ethanol preparation of DNA and RNA --- p.p.50
Chapter 2.11.6 --- Agarose gel electrophoresis of DNA --- p.p.51
Chapter 2.12 --- Statistical methods --- p.p.52
Chapter CHAPTER 3 --- Estrogenic and antiproliferative activities on MCF-7 breast cancer cells by flavonoids
Chapter 3.1 --- Introduction --- p.p.53
Chapter 3.2 --- Results --- p.p.56
Screening of phytoestrogens for estrogenic activities on MELN cells --- p.p.56
Cell proliferation activity of phytoestrogens on MCF-7 and MDA-MA231 cells --- p.p.59
Estrogenic and antiestrogenic activity of phytoestrogens on ERα or erβ transfected hepg2 cells --- p.p.64
Chapter 3.3 --- Discussion --- p.p.73
Chapter Chapter 4 --- interaction of baicalein with estrogen receptors
Chapter 4.1 --- Introduction --- p.p.76
Chapter 4.2 --- Results --- p.p.78
Estrogen receptor competition assay --- p.p.78
ERE-Luciferase gene reporter assay --- p.p.82
Chapter 4.3 --- Discussion --- p.p.88
Chapter Chapter 5 --- baicalein and genistein display differential actions on er transactivation
Chapter 5.1 --- Introduction --- p.p.90
Chapter 5.2 --- Results --- p.p.92
Estrogenic and antiestrogenic activities of genistein and baicalein on ER transactivation --- p.p.92
Chapter 5.3 --- Discussion --- p.p.105
Chapter CHAPTER 6 --- APOPTOTIC EFFECTS OF BAICALEIN ON MCF-7 AND MDA-MB-231 CELL LINES
Chapter 6.1 --- Introduction --- p.p.107
Chapter 6.2 --- Results --- p.p.111
ER POSITIVE MCF-7 AND ER NEGATIVE MDA-MB-231 cell death assay --- p.p.111
"Bcl-2, Bax and PS2 mRNA expression " --- p.p.116
Arrest at sub G1 phase of MCF-7 by baicalein --- p.p.124
Chapter 6.3 --- Discussion --- p.p.127
Chapter CHAPTER 7 --- BAICALEIN CAN REDUCE INTRACELLULAR cholesterol and triglceride
Chapter 5.1 --- Introduction --- p.p.129
Chapter 5.2 --- Results --- p.p.130
Baicalein has beneficial effect on lipid metabolism --- p.p.130
Chapter 5.3 --- Discussion --- p.p.139
Chapter chapter 8 --- Summary --- p.p.140
BIBLIOGRAPHY --- p.p.142
APPENDIX 1 ABBREVIATIONS --- p.p.153
APPENDIX 2 PRIMER LISTS --- p.p.156
APPENDIX 3 REAGENTS AND BUFFERS --- p.p.157
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Ching, Hsu-Yu, and 許玉青. "Effects of Arsenics on Cell Growth and Estrogen Receptor-αExpression in MCF-7 Breast Cancer Cells." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/07624442190395469629.
Full textAbstract:
碩士國立臺灣師範大學
生命科學研究所
93
Inorganic arsenics, the common environmental pollutants, are widely dispersed and the well-documented human carcinogens associated with cancers of skin, lung and bladder and can induce cytotoxicity, chromosomal abnormalities, oxidative stress, altered DNA repair, altered growth factors etc. Several reports indicated that inorganic arsenic might somehow act through an estrogenic mode of action. In this study, effects of sodium arsenite and sodium arsenate on cytotoxicity, cell proliferation and the expression of estrogen receptorα(ERα) in breast adenocarcinoma MCF-7 cells are determinated. The preliminary results show that the inhibiting threshold concentrations of sodium arsenite and sodium arsenate on cell growth are at 1μM and 10μM, respectively, whereas their concentrations lower than inhibiting threshold concentrations promoted cell growth instead of cell toxicity. Time course studies on cells treated with 0.1~1μM sodium arsenite and 1~10μM sodium arsenate for 24 h, and observed consecutive six days without drugs, MCF-7 cells proliferation exhibited continuous increase. Cotreated with drugs and estrogen antagoist (ICI 182,780), MCF-7 cell proliferations were completely inhibited. Data of Western blotting show that the expression of ERα were decreased in cells treated with low dose of sodium arsenite and sodium arsenate, but expression of estrogen receptorβ were not affected. Immunocytochemical studies with fluorescent microscopy illustrated that ERα displayed a diffusion distribution in cytoplasm and were more concentrated within nucleus of control cell and E2-treated cells. In arsenic-treated cells, the ERαonly displayed in cytoplasm. Whole-cell competitive estrogen-receptor binding assay demonstrate that 0.1, 0.5 and 1μM sodium arsenite could bound with 28%, 35% and 48% in ER respectively. In this study it was concluded that arsenite could bind with estrogen receptor. Based on results above, MCF-7 cells treated with a low dose sodium arsenite and sodium arsenate affect cell proliferation, ERαexpression, and competition of estrogen receptor binding；and indicate that inorganic arsenics do have the characteristics of environmental hormone for inducing physiological effect, through a estrogen model.
48
Warrington, Jenny. "Effect of Consumption of Selenium-Enriched Milk Proteins on Human Mammary Tumor Progression." Thesis, 2013. http://hdl.handle.net/10214/6610.
Full textAbstract:
Selenium, an essential trace mineral that becomes anticarcinogenic at supranutritional levels, is readily incorporated into milk proteins when cows are fed high levels of selenium. The objective of this study was to investigate the effects of selenized milk protein on human mammary tumor progression. Four isonitrogenous diets with Se levels of 0.16, 0.51, 0.85 and 1.15 ppm were formulated by mixing low- and high-selenium milk protein isolates with a rodent premix. MCF-7 human breast cancer cells were inoculated into the mammary fat pad of female BALB/c nude mice implanted with slow-release 17 β-estradiol pellets. Mice with palpable tumors were randomly assigned to one of four diets for 10 weeks. Increasing Se intake reduced final tumor volume and the number of tumors > 500 mm3 in volume. There was a two-fold higher proportion of apoptotic cells in tumors exposed to the highest Se level.Financial support was provided by Dairy Farmers of Ontario, Alltech Canada, Inc., and NSERC Canada.
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Azevedo, Cláudia Filipa Maia. "The Effect of Dietary Polyphenols on Glucose Uptake by Breast Cancer Cells (MCF-7)." Dissertação, 2013. https://repositorio-aberto.up.pt/handle/10216/70537.
Full text
50
Chen, Wei-Chih, and 陳韋志. "Iron Chelators Modulate Anti-Proliferation and Apoptosis in Human Breast Cancer MCF-7 Cells." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/83754911050539494783.
Full textAbstract:
碩士輔仁大學
營養科學系碩士班
103
Neoplastic cells have a higher capacity of iron uptake than normal cell, and require more iron content due to their rapid cell growth. Depletion of cellular iron by using iron chelator have been shown to inhibit the cell growth and/or to induce the apoptosis for many malignant cell lines, however the detailed molecular mechanisms are far from clear in the proteomic scale. Our previous study found iron chelator deferoxamine simultaneously mediated the expression of the cell growth and apoptotic associated proteins using dimethyl labeling coupled with mass spectrometry. Therefore, the aim of our study was to investigate the molecular mechanism of cell apoptosis induced by iron chelator in MCF-7 cells. After deferoxamine (DFO) treatment, the BrdU incorporating capacity was decreased, and the percentage of apoptosis increased in time dependent manner. The nuclear version of p53, Ap-2γ and prohibitin levels were increased in DFO-treated MCF-7 cells. In contrast, DFO treatment decreased the nuclear p21, TCTP, Apaf-1 levels in MCF-7 cells. Further, nuclear PELP1 interacts with p53, functions as p53-coactivator and p53 forms a complex with Ap-2γ and TCTP .Taken together, iron chelator deferoxamine decreases proliferation and induces apoptosis may be through the up-regulation of p53 that forms a complex with Ap-2γ and TCTP to up-regulation of Ap-2γ and down-regulation of TCTP.