Technical Details:
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.
Looking for Partners:
Isogenic cell lines with or without intact BAX genes are valuable reagents for studying apoptosis induced by anticancer agents in human cancer cells. They can also be used for identifying novel small molecules that are dependent on BAX to induce apoptosis in human cancer cells, which can potentially be used as chemotherapeutic or chemopreventive agents.
