Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis

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

doi:10.1073/pnas.95.2.681

Paper Title

Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis

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Journal

Proceedings of the National Academy of Sciences of the United States of America

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DOI

10.1073/pnas.95.2.681

Publication Info

Volume: 95 | Issue: 2 | Pages: 681-686

Published On

December, 1998

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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.