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-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.
Rigas
Basil
B
Division of Cancer Prevention, Department of Medicine, SUNY at Stony Brook, Stony Brook, NY 11794-8160, USA. brigas@notes.cc.sunysb.edu
Kashfi
Khosrow
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020030:Nitric Oxide Donors / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020030:Nitric Oxide Donors