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[Cancer Research 61, 3285-3289, April 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Nitric Oxide-releasing Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Alter the Kinetics of Human Colon Cancer Cell Lines More Effectively than Traditional NSAIDs

Implications for Colon Cancer Chemoprevention1

Jennie L. Williams, Simona Borgo, Izhar Hasan, Eddy Castillo, Frank Traganos and Basil Rigas2

American Health Foundation, Valhalla, New York 06595 [J. L. W., B. R.]; Division of Gastroenterology [J. L. W., I. H., E. C., B. R.] and Brader Cancer Canter [F. T.], New York Medical College, Valhalla, New York 06595; and Strang Cancer Prevention Center [S. B.] and Rockefeller University [B. R.], New York, New York 10021

Nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs), consisting of a known nonsteroidal anti-inflammatory drug (NSAID) and a nitric oxide (NO)-releasing group, are reported safer than NSAIDs. To assess their potential in colon cancer chemoprevention, we studied in vitro the effect of NO-aspirin, NO-sulindac, and NO-ibuprofen on colonocyte kinetics. These three NO-NSAIDs reduced the growth of cultured HT-29 colon adenocarcinoma cells much more effectively than the corresponding NSAIDs; e.g., at 24 h, their IC50 values were as follows: (a) aspirin, >5000 µM; (b) NO-aspirin, 1 µM; (c) sulindac, 750 µM; (d) NO-sulindac, 150 µM; (e) ibuprofen, >1000 µM; and (f) NO-ibuprofen, 42 µM. This effect was due to inhibition of proliferation and induction of apoptosis and perhaps to the induction of novel cell changes, characterized by extensive DNA degradation. NO-NSAIDs also blocked the G0-G1 to S cell cycle transition. Their superior effectiveness compared with traditional NSAIDs, combined with their reported safety, makes them promising candidates for chemopreventive agents against colon cancer.




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Copyright © 2001 by the American Association for Cancer Research.