SMAC/Diablo-dependent apoptosis induced by nonsteroidal antiinflammatory drugs (NSAIDs) in colon cancer cells

Manu Kohli, Jian Yu, Craig Seaman, Alberto Bardelli, Kenneth W. Kinzler, Bert Vogelstein, Christoph Lengauer, Lin Zhang

Research output: Contribution to journalArticle

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 pl (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.

Original languageEnglish
Pages (from-to)16897-16902
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number48
DOIs
Publication statusPublished - Nov 30 2004

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ASJC Scopus subject areas

  • Genetics
  • General

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