Role of BAX in the apoptotic response to anticancer agents

To assess the role of BAX in drug-induced apoptosis in human colorectal can cer cells, we generated cells that Lack functional BAX genes. Such cells we re partially resistant to the apoptotic effects of the chemotherapeutic age nt 5-fluorouracil, but apoptosis was not abolished. In contrast, the absenc e of BAX completely abolished the apoptotic response to the chemopreventive agent sulindac and other nonsteroidal anti-inflammatory drugs (NSAIDs). NS AIDs inhibited the expression of the antiapoptotic protein Bcl-X-L, resulti ng in an altered ratio of BAX to BcL-X-L and subsequent mitochondria-mediat ed cell death. These results establish an unambiguous role for BAX in apopt otic processes in human epithelial cancers and may have implications for ca ncer chemoprevention strategies.