NSAIDs Downregulate Bcl-XL and Dissociate BAX and Bcl-XL to Induce Apoptosis in Colon Cancer Cells

Authors: Bank, Alexander¹; Yu, Jian²; Zhang, Lin¹

Source: Nutrition and Cancer, Volume 60, Supplement 1, 2008 , pp. 98-103(6)

Publisher: Routledge, part of the Taylor & Francis Group

Buy & download fulltext article:

Price: $50.43 plus tax (Refund Policy)

Abstract:

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-XL) in colon cancer cells. In this study, we further investigated how BAX and Bcl-XL mediate NSAID-induced apoptosis. We found that Bcl-XL is downregulated by NSAIDs in part through proteasome-mediated protein degradation. NSAIDs promote the dissociation of BAX and Bcl-XL 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-XL, thereby promoting BAX mitochondrial translocation and multimerization.

Document Type: Research article

DOI: http://dx.doi.org/10.1080/01635580802381261

Affiliations: 1: University of Pittsburgh Cancer Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA 2: University of Pittsburgh Cancer Institute and Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Publication date: 2008-01-01