Elsevier

Medical Hypotheses

Volume 54, Issue 2, February 2000, Pages 210-215
Medical Hypotheses

Regular Article
Is inhibition of cyclooxygenase required for the chemopreventive effect of NSAIDs in colon cancer? A model reconciling the current contradiction

https://doi.org/10.1054/mehy.1999.0023Get rights and content

Abstract

NSAIDs are powerful chemopreventive agents for colon cancer, but their mechanism of action remains unknown. Their best recognized pharmacological property is inhibition of the enzyme cyclooxygenase (COX), which catalyzes the synthesis of prostaglandins; however, additional effects are well documented. Current studies on the mechanism of the chemopreventive effect of NSAIDs lead to two contradictory conclusions: NSAIDs prevent colon cancer either by inhibiting the activity of COX, or through mechanisms that do not require COX inhibition. To resolve this apparent conflict, after examining several alternatives, we propose a model, which assumes that both mechanisms are correct but that they exert their effect either on different steps of the multistep process of colon carcinogenesis or on different control mechanisms. This postulated dual action of NSAIDs may explain their remarkable effectiveness in colon cancer prevention. Unraveling these mechanistic details can be very rewarding for the design of more refined approaches to cancer chemoprevention and for a deeper understanding of colorectal carcinogenesis.

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    Support: NIH CA73298 and CA29502 (Clinical Nutrition Research Unit-New Investigator Award), American Institute for Cancer Research 95B043, and The Arthur and Rochelle Belfer Foundation.

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