Nitric oxide induces cyclooxygenase expression and inhibits cell growth in colon cancer cell lines.

The role of nitric oxide (NO) in colon cancer remains controversial. Inducible nitric oxide synthase (iNOS) has been reported to be up regulated and down regulated in colorectal cancer in both animal models and patient tissue samples. Cyclooxygenase-2 (COX-2) is important in colorectal carcinogenesis but its relationship with NO has never been studied in colon cancer. Three colon cancer cell lines (HCA7, HT29 and HCT116) with different COX-2 expression and activities were used to study the effect of the NO donor, S-nitrosoglutathione (GSNO). The effects of GSNO (10-500 micro M) on cell growth, PGE(2) production, COX-1/COX-2 protein expression and cell-cycle distribution were evaluated. GSNO increased PGE(2) production and induced COX-1 and COX-2 protein expression in a dose- and time-dependent manner. Higher concentrations of GSNO also inhibited cell growth and induced apoptosis in all three cell lines, regardless of their COX-2 expression/activities. Inhibition of PGE(2) production did not further improve the inhibitory effect of GSNO.