Aspirin Research Today is a free monthly online journal that collates and summarizes the latest research about Aspirin, including details on acetylsalicylic acid, baby aspirin, side effects, overdose, allergy.

NO-donating aspirin inhibits both the expression and catalytic activity of inducible nitric oxide synthase in HT-29 human colon cancer cells.

Spiegel A, Hundley TR, Chen J, Gao J, Ouyang N, Liu X, Go MF, Tsioulias GJ, Kashfi K, Rigas B

Division of Cancer Prevention, SUNY at Stony Brook, Stony Brook, NY 11794-5200, USA.

Nitric oxide-releasing aspirin (NO-ASA) is emerging as a potentially important chemopreventive agent against colon cancer. We examined in HT-29 human colon adenocarcinoma cells the effect of NO-ASA on the inducible form of nitric oxide synthase (NOS2), an enzyme implicated in colon carcinogenesis. NO-ASA inhibited in a time- and concentration-dependent manner the expression of NOS2 up to 70% compared to control (IC50 for this effect = 46 microM). NO-ASA also decreased the corresponding steady-state mRNA levels and this reduction preceded the reduction of protein levels by at least 6 h. NO-ASA also reduced the enzymatic activity of NOS2, as determined by a direct enzyme assay (maximal reduction = 80%) and by determining the accumulation of NO in the culture medium (IC50 for this effect = 36 microM). These effects of NO-ASA on NOS2 were paralleled by inhibition in cell growth (IC50 = 8.5 microM). These findings indicate that NO-ASA profoundly inhibits both the expression and enzymatic activity of NOS2 and suggest that these effects may represent an important mechanism for the colon cancer chemopreventive effect of NO-ASA.

Published 12 September 2005 in Biochem Pharmacol, 70(7): 993-1000.
Full-text of this article is available online (may require subscription).

© 2004-2008 Aspirin Research Today. All Rights Reserved.