PMID: 11902503Mar 21, 2002Paper

Nonsteroidal anti-inflammatory drugs, apoptosis, and colon-cancer chemoprevention

The Lancet Oncology
Timothy A Chan

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) can inhibit colorectal tumorigenesis and are among the few agents known to be chemopreventive. Epidemiological studies and experiments with animals have shown that NSAIDs have powerful anticolorectal cancer properties, but the mechanism of these effects remains unclear. NSAIDs can inhibit neoplastic growth by inducing apoptosis in cancer cells; the way they do this is currently an area of intense investigation. The most well-characterised pharmacological feature of NSAIDs is their inhibition of the enzyme cyclo-oxygenase (COX), which catalyses the synthesis of prostaglandins. Several studies have shown that COX inhibition prevents cell proliferation and promotes apoptosis. The chemopreventive effects of NSAIDs are thought to occur via this pathway. Other observations indicate that NSAIDs also promote apoptosis through mechanisms that are independent of COX inhibition. This idea is supported by the finding that compounds that are structurally similar to NSAIDs, but do not inhibit COX, also have chemopreventive and proapoptotic properties. COX-dependent and COX-independent mechanisms of apoptosis induction are not mutually exclusive, and it is likely that both have a role in the biolo...Continue Reading

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