An assessment of taxol-Induced apoptosis in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells

Butt, Krista (2004) An assessment of taxol-Induced apoptosis in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. Masters thesis, Memorial University of Newfoundland.

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Abstract

The ability of taxol to induce apoptosis was compared in phenotypically dissimilar MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. To assess this, morphological examination, PARP cleavage, and TUNEL assay was employed. Treatment of these cells with 100 nM taxol led to chromatin condensation, DNA fragmentation, and apoptosis-associated morphological changes after 3-24 hours exposure. Additionally, proteolytic cleavage of poly (ADP-ribose) polymerase was detected in MCF-7 but not MDA-MB-231 cells. To further elucidate these findings, the expression of certain apoptotic regulatory genes was also examined by western blot analysis. In MCF-7 cells, levels of Bcl-2 and p53 increased after 24 hours and 72 hours, respectively, whereas no significant change in levels of cytochrome c was found. Conversely, in MDA-MB-231 cells, levels of Bcl-2 and p53 decreased after 72 hours, whereas cytochrome c levels increased after 72 hours. These data suggest that 100 nM taxol induces apoptosis in MCF-7 and MDA-MB-231 cells, probably via a p53-dependent and independent pathway, respectively. Bcl-2 and cytochrome c, however, did not play clear roles. Increased understanding of taxol-induced apoptosis may lead to the development of more effective taxol-based chemotherapy regimens and improved clinical responses

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