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Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance

Item Type:Article
Title:Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance
Creators Name:Friedrich, K. and Wieder, T. and von Haefen, C. and Radetzki, S. and Jaenicke, R. and Schulze-Osthoff, K. and Doerken, B. and Daniel, P.T.
Abstract:In this study, we asked whether overexpression of caspase-3, a central downstream executioner of apoptotic pathways, might sensitize breast cancer cells with acquired drug resistance (MT1/ADR) to drug-induced apoptosis. As control, we employed caspase-3 negative and caspase-3-transfected MCF-7 cells. Whereas mock-transfected MCF-7 cells were resistent to epirubicin, etoposide and paclitaxel (taxol), the same drugs led to breakdown of nuclear DNA in caspase-3-transfected MCF-7 cells. MT1/ADR cells express low levels of wild type caspase-3 but show defective caspase activation and apoptosis upon drug exposure. These cells also display a less efficient activation of the mitochondrial permeability transition. Caspase-3-transfected MT1/ADR clones showed a 2.8-fold increase in the protein level and a 3.7-fold higher specific enzyme activity. Procaspase-3 overexpression was not toxic and did not affect background apoptosis. Interestingly, procaspase-3-transfected MT1/ADR cells were more sensitive to cytotoxic drugs as compared with vector-transfected controls and DNA fragmentation nearly reached the levels of the original drug sensitive MT1 cells. Thus, overexpression of caspase-3 enhances chemosensitivity especially in situations where activation of the mitochondrial apoptosome is disturbed.
Keywords:Caspase-3, Chemotherapeutics, Apoptosis, Drug Resistance, MCF-7 Cells
Source:Oncogene
ISSN:0950-9232
Publisher:Nature Publishing Group (U.K.)
Volume:20
Number:22
Page Range:2749-2760
Date:17 May 2001
Official Publication:http://www.nature.com/onc/journal/v20/n22/abs/1204342a.html
PubMed:View item in PubMed

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