Nitric-oxide-donating NSAIDs as agents for cancer prevention.

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.

• Authors: Basil Rigas, Khosrow Kashfi
• Journal: Trends in molecular medicine (Trends Mol Med) Vol. 10 Issue 7 Pg. 324-30 (Jul 2004) ISSN: 1471-4914 [Print] England
• PMID: 15242680 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Nitric Oxide Donors

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Humans
• Neoplasms (drug therapy, metabolism, pathology)
• Nitric Oxide Donors (therapeutic use)