Proapoptotic anti-inflammatory drugs

The very fact that apoptosis and nonsteroidal anti-inflammatory drugs (NSAI Ds) can be linked in the same title should tell lieu that something unusual is happening. The image of NSAIDs among physicians is certainly discordant with that associated with cancer treatment, which usually involves adminis tration of drugs with serious or even life-threatening toxicity. In contras t, the drugs discussed in this review, including selective cyclooxygenase-a inhibitors, lipoxygenase inhibitors, and novel NSAID derivatives (eg, suli ndac sulfone and R-flurbiprofen), offer the promise of oral, nontoxic agent s able to control the progression of established prostate cancer and possib ly to prevent the development of prostate cancer de novo. NSAIDs were initi ally developed to suppress inflammation and pain by inhibiting the producti on of prostaglandin E2 and its metabolites. At first glance, the fact that NSAIDs are active against prostate cancer in laboratory and clinical studie s might suggest that prostaglandins play a pivotal role in prostate cancer biology. However, the story is much more complex than that. Although cycloo xygenase-mediated production of prostaglandins appears to play an important role in the biology of prostate cancer, the NSAIDs and derivatives with pr omising activity against prostate cancer manifest several mechanisms of act ion that can include direct inhibition of eicosanoid formation, indirect in hibition of eicosanoid formation by inhibiting expression of enzymes involv ed in eicosanoid synthesis, or by interfering with the function of cyclic g uanosine monophosphate. (C) 2001, Elsevier Science inc.