Role of BAX in the apoptotic response to anticancer agents
1Howard Hughes Medical Institute, Oncology Center, and Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
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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