Role of BAX in the apoptotic response to anticancer agents |
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Authors: | Zhang L Yu J Park B H Kinzler K W Vogelstein B |
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Institution: | Howard Hughes Medical Institute, Oncology Center, and Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. |
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Abstract: | To assess the role of BAX in drug-induced apoptosis in human colorectal cancer cells, we generated cells that lack functional BAX genes. Such cells were partially resistant to the apoptotic effects of the chemotherapeutic agent 5-fluorouracil, but apoptosis was not abolished. In contrast, the absence of BAX completely abolished the apoptotic response to the chemopreventive agent sulindac and other nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibited the expression of the antiapoptotic protein Bcl-XL, resulting in an altered ratio of BAX to Bcl-XL and subsequent mitochondria-mediated cell death. These results establish an unambiguous role for BAX in apoptotic processes in human epithelial cancers and may have implications for cancer chemoprevention strategies. |
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