Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis

Timothy A. Chan, Patrice J. Morin, Bert Vogelstein, Kenneth W. Kinzler

Research output: Contribution to journalArticlepeer-review

554 Scopus citations

Abstract

Nonsteroidal antiinflammatory drugs (NSAIDs) can inhibit colorectal tumorigenesis and are among the few agents known to be useful for the chemoprevention of neoplasia. Here, we show that the tumor suppressive effects of NSAIDs are not likely to be related to a reduction in prostaglandins but rather are due to the elevation of the prostaglandin precursor arachidonic acid (AA). NSAID treatment of colon tumor cells results in a dramatic increase in AA that in turn stimulates the conversion of sphingomyelin to ceramide, a known mediator of apoptosis. These results have significant implications for understanding and improving colon cancer chemoprevention.

Original languageEnglish (US)
Pages (from-to)681-686
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number2
DOIs
StatePublished - Jan 20 1998

ASJC Scopus subject areas

  • General

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