PROSTAGLANDIN-H SYNTHASES, NONSTEROIDAL ANTIINFLAMMATORY DRUGS, AND COLON-CANCER

Members of the structurally diverse class of drugs known as nonsteroid al anti-inflammatory drugs (NSAIDs) have the ability to prevent or red uce the occurrence of colorectal, certain other gastrointestinal, and perhaps other cancers, The anticarcinogenic property of NSAIDs has bee n shown in epidemiological studies with humans and in experimental car cinogenesis studies with animals, In addition, clinical studies of the human disease familial adenomatous polyposis have demonstrated the ef ficacy of NSAIDs in mediating regression of colorectal adenomas, The m echanism of the anticarcinogenic effect of these drugs is not known, b ut most hypotheses have involved the common property of the NSAIDs to inhibit prostaglandin synthase (PHS) enzymes and thereby cause a subse quent reduction in levels of prostaglandins (PG) in tissue, Recent rep orts have questioned the role of PHS inhibition in the anticarcinogeni c activity of NSAIDs by showing that some NSAID-related compounds that are not PHS inhibitors can induce the same anticarcinogenic changes i n cell cycle and apoptotic response as the PHS inhibitors, In this rev iew we will examine the evidence that NSAIDs are anticarcinogenic, the evidence supporting PBS as the target of NSAIDs, and the evidence for and against inhibition of PG synthesis as the mechanism of cancer pre vention by NSAIDs.-Levy, G. N. Prostaglandin H synthases, nonsteroidal anti-inflammatory drugs, and colon cancer.