Role of BAX in the Apoptotic Response to Anticancer Agents
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- 3 November 2000
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 290 (5493) , 989-992
- https://doi.org/10.1126/science.290.5493.989
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 forBAX in apoptotic processes in human epithelial cancers and may have implications for cancer chemoprevention strategies.Keywords
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