Nitric-oxide-donating NSAIDs as agents for cancer prevention

Nitric-oxide-donating nonsteroidal anti-inflammatory drugs (NO–NSAIDs), which consist of an NSAID with an NO-donating moiety covalently attached to it, promise to contribute significantly towards the development of effective chemoprevention strategies against cancer. NO–NSAIDs inhibit the growth of cultured cancer cells 10–6000-fold more potently than their parent NSAIDs and prevent colon cancer in animal tumor models. Clinical data indicate that they are extremely safe. Mechanistically, NO–aspirin, the best-studied NO–NSAID, has pleiotropic effects on cell signaling (it inhibits Wnt signaling, induces nitric oxide synthase and NF-κB activation and induces cyxlooxygenase-2 expression), and this mechanistic redundancy might be central to its mode of action against cancer. The apparent safety and superior efficacy of NO–NSAIDs makes them promising chemopreventive agents against cancer.