NSAIDs Downregulate Bcl-XL and Dissociate BAX and Bcl-XL to Induce Apoptosis in Colon Cancer Cells
NSAIDs Downregulate Bcl-XL and Dissociate BAX and Bcl-XL to Induce Apoptosis in Colon Cancer Cells
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DOI：
10.1080/01635580802381261
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发表时间：
2008-01-01
影响因子：
2.9
通讯作者：
Zhang, Lin
中科院分区：
文献类型：
--
作者：
Bank, Alexander;Yu, Jian;Zhang, Lin
Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in preventing colorectal cancer. Apoptosis induction by NSAIDs plays a critical role in NSAID-mediated chemoprevention. Our previous study demonstrated that NSAIDs require the proapoptotic B-cell non-Hodgkin lymphoma-2 (Bcl-2) family member Bcl-2-associated x protein (BAX) to induce apoptosis and inhibit the expression of antiapoptotic basal cell lymphoma-extra large (Bcl-X-L) in colon cancer cells. In this study, we further investigated how BAX and Bcl-X-L mediate NSAID-induced apoptosis. We found that Bcl-X-L is downregulated by NSAIDs in part through proteasome-mediated protein degradation. NSAIDs promote the dissociation of BAX and Bcl-X-L and translocation of BAX to the mitochondria. Furthermore, we found that only wild-type BAX, but not a mutant BAX deficient in either protein-protein interaction or mitochondrial localization, was able to restore NSAID-induced apoptosis in the BAX-knockout colon cancer cells. These results suggest that NSAIDs induce apoptosis in colon cancer cells by dissociating BAX and Bcl-X-L, thereby promoting BAX mitochondrial translocation and multimerization.
