A Fas-associated Death Domain Protein-dependent Mechanism Mediates the Apoptotic Action of Non-steroidal Anti-inflammatory Drugs in the Human Leukemic Jurkat Cell Line

Zhiyong Han, Panayotis Pantazis, James H. Wyche, Nichola Kouttab, Vincent J. Kidd, Eric A. Hendrickson

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are inhibitors of cyclooxygenase-1 and -2 and are useful for prevention and cure of cancers, especially colon and rectal cancers. The NSAIDs indomethacin and sulindac sulfide have been shown to induce apoptosis of colon epithelial cancer cells by a Bax-dependent mechanism that involves mitochondria-mediated activation of a caspase-9-dependent pathway. In this report, we demonstrate that indomethacin and sulindac sulfide induce apoptosis of human leukemic Jurkat cells by a mechanism that requires the Fas-associated Death Domain Protein-mediated activation of a caspase-8-dependent pathway. Therefore, NSAIDs induce apoptosis by different mechanisms depending on the cell type.

Original languageEnglish (US)
Pages (from-to)38748-38754
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number42
DOIs
StatePublished - Oct 19 2001

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