NO (nitric oxide) biology has provided the impetus for the development of anticancer agents based on their ability to release NO. NO-NSAIDs (NO-donating non-steroidal anti-inflammatory drugs), consisting of a conventional NSAID to which an NO-releasing moiety is covalently attached, are promising chemopreventive agents against cancer. Compared with their parent compounds, NO-NSAIDs are up to several hundred times more potent in inhibiting the growth of cancer cell lines and prevent colon and pancreatic cancer in animal models. Their chemopreventive effect is due to inhibition of proliferation, induction of cell death and inhibition of cell-cycle-phase transitions. NO-ASA (NO-aspirin), the best-studied NO-NSAID, induces oxidative stress in target cells. Major downstream signalling effects involve the Wnt, NOS2 (nitric oxide synthase 2), MAPK (mitogen-activated protein kinase), NF-κB (nuclear factor κB) and Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2) pathways. NO-NSAIDs, particularly NO-ASA, appear to be safe compounds, as suggested by many animal and early human studies. An ongoing clinical trial is designed to determine whether NO-ASA can inhibit early stages of colon carcinogenesis in subjects at risk for colon cancer. It is clinical trials that will ultimately determine the role of NO-NSAIDs in cancer prevention and perhaps treatment.
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November 2007
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Conference Article|
October 25 2007
Novel agents for cancer prevention based on nitric oxide
B. Rigas
B. Rigas
1
1Division of Cancer Prevention, Stony Brook University, Stony Brook, NY 11794-5200, U.S.A.
1email basil.rigas@stonybrook.edu
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Publisher: Portland Press Ltd
Received:
June 11 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (5): 1364–1368.
Article history
Received:
June 11 2007
Citation
B. Rigas; Novel agents for cancer prevention based on nitric oxide. Biochem Soc Trans 1 November 2007; 35 (5): 1364–1368. doi: https://doi.org/10.1042/BST0351364
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