The use of nitric oxide-donating nonsteroidal anti-inflammatory drugs in the chemoprevention of colorectal neoplasia.
OBJECTIVE
Nitric oxide-donating nonsteroidal anti-inflammatory drugs are emerging as a promising class of compounds for the chemoprevention of colon cancer. Recent progress in their preclinical and mechanistic evaluation is reviewed.


RESULTS
Compared to their parent compounds, nitric oxide-donating nonsteroidal anti-inflammatory drugs are up to several hundred times more potent in inhibiting the growth of colon cancer cell lines and also quite effective in preventing colon cancer in various tumor animal models. Their chemopreventive effect is brought about through a strong cell kinetic effect, including inhibition of proliferation, induction of cell death and inhibition of cell cycle phase transitions. The induction of oxidative stress appears mechanistically crucial. Pleiotropic effects on cell signaling have been identified including Wnt, NOS2, mitogen-activated protein kinase and Nrf2 signaling. Nitric oxide-donating nonsteroidal anti-inflammatory drugs, particularly nitric oxide-donating aspirin, appear to be very safe compounds, as evidenced from many animal and early human studies.


CONCLUSIONS
Nitric oxide-donating nonsteroidal anti-inflammatory drugs hold the promise of being safe and effective chemopreventive agents against colon cancer. Clinical trials are needed to determine whether these drugs can be applied clinically.
Rigas
Basil
B
Division of Cancer Prevention and Gastroenterology, Department of Medicine, Stony Brook University, Stony Brook, New York 11794, USA. basil.rigas@stonybrook.edu
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D006801:Humans; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009569:Nitric Oxide