Nitric-oxide-donating NSAIDs as agents for cancer prevention |
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Authors: | Rigas Basil Kashfi Khosrow |
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Institution: | Division of Cancer Prevention, Department of Medicine, SUNY at Stony Brook, Stony Brook, NY 11794-8160, USA. brigas@notes.cc.sunysb.edu |
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Abstract: | 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-kappaB activation and induces cyclooxygenase-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. |
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