Members of the structurally diverse class of drugs known as nonsteroidal anti-inflammatory drugs (
NSAIDs) have the ability to prevent or reduce the occurrence of colorectal, certain other gastrointestinal, and perhaps other
cancers. The anticarcinogenic property of
NSAIDs has been shown in epidemiological studies with humans and in experimental
carcinogenesis studies with animals. In addition, clinical studies of the human disease
familial adenomatous polyposis have demonstrated the efficacy of
NSAIDs in mediating regression of colorectal
adenomas. The mechanism of the
anticarcinogenic effect of these drugs is not known, but most hypotheses have involved the common property of the
NSAIDs to inhibit
prostaglandin synthase (PHS)
enzymes and thereby cause a subsequent reduction in levels of
prostaglandins (PG) in tissue. Recent reports have questioned the role of PHS inhibition in the anticarcinogenic activity of
NSAIDs by showing that some
NSAID-related compounds that are not PHS inhibitors can induce the same anticarcinogenic changes in cell cycle and apoptotic response as the PHS inhibitors. In this review we will examine the evidence that
NSAIDs are anticarcinogenic, the evidence supporting PHS as the target of
NSAIDs, and the evidence for and against inhibition of PG synthesis as the mechanism of
cancer prevention by
NSAIDs.