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Role of BAX in the Apoptotic Response to Anticancer Agents

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Science  03 Nov 2000:
Vol. 290, Issue 5493, pp. 989-992
DOI: 10.1126/science.290.5493.989

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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 forBAX in apoptotic processes in human epithelial cancers and may have implications for cancer chemoprevention strategies.

  • * To whom correspondence should be addressed. E-mail: vogelbe{at}welch.jhu.edu

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