| Literature DB >> 15557007 |
Manu Kohli1, Jian Yu, Craig Seaman, Alberto Bardelli, Kenneth W Kinzler, Bert Vogelstein, Christoph Lengauer, Lin Zhang.
Abstract
Nonsteroidal antiinflammatory drugs (NSAIDs) form a paradigm for the chemoprevention of cancer, preventing colonic tumor progression in both experimental animals and humans. However, the mechanisms underlying the antineoplastic effects of NSAIDs are currently unclear. We found that the mitochondrial second mitochondrial-derived activator of caspase (SMAC)/direct inhibitor of apoptosis protein-binding protein with low pI (Diablo) protein translocates into the cytosol during NSAID-induced apoptosis in colon cancer cells. When SMAC/Diablo is disrupted by homologous recombination and RNA interference in these cells, the NSAID-induced apoptosis is abrogated. Biochemical markers of apoptosis, such as caspase activation, cytosolic release of cytochrome c and apoptosis-inducing factor, and mitochondrial membrane potential change, are accordingly decreased. These results establish that SMAC/Diablo is essential for the apoptosis induced by NSAIDs in colon cancer cells.Entities:
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Year: 2004 PMID： 15557007 PMCID： PMC534714 DOI： 10.1073/pnas.0403405101
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205