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PMID: 9435252 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 2 ·1998-01-20 ·Pages 681-6

Chan TA, Morin PJ, Vogelstein B, Kinzler KW

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.

MeSH Terms
Anti-Inflammatory Agents, Non-Steroidal/pharmacology Apoptosis/drug effects Arachidonic Acid/metabolism Colorectal Neoplasms/metabolism,pathology Humans Prostaglandins/metabolism Tumor Cells, Cultured
Chemicals
Anti-Inflammatory Agents, Non-Steroidal Prostaglandins Arachidonic Acid
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chan T A
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Morin P J
Vogelstein B
Kinzler K W
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43 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.2.681
Published
1998-01-20
Pages
681-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18480
Subset
IM
Grants
NCI NIH HHS · CA57345 · United States
NCI NIH HHS · P50 CA062924 · United States
NCI NIH HHS · CA62924 · United States
NCI NIH HHS · R37 CA057345 · United States
NCI NIH HHS · R01 CA057345 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.2.681 PMC Full Text View journal details
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