MECHANISMS UNDERLYING NONSTEROIDAL ANTIINFLAMMATORY DRUG-MEDIATED APOPTOSIS

Nonsteroidal antiinflammatory drugs (NSAIDs) can inhibit colorectal tu morigenesis and are among the few agents known to be useful for the ch emoprevention of neoplasia. Here, we show that the tumor suppressive e ffects of NSAIDs are not likely to be related to a reduction in prosta glandins but rather are due to the elevation of the prostaglandin prec ursor arachidonic acid (AA). NSAID treatment of colon tumor cells resu lts in a dramatic increase in AA that in turn stimulates the conversio n of sphingomyelin to ceramide, a known mediator of apoptosis. These r esults have significant implications for understanding and improving c olon cancer chemoprevention.