Suppression of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells by chemopreventive agents with a resorcin-type structure

Cyclooxygenase-2 (COX-2) is abundantly expressed in colon cancer cells. It has been reported that inhibition of COX-2 enzyme activity is shown to prev ent colon carcinogenesis. Thus, suppression of COX-2 expression may also be an effective chemopreventive strategy, In the present study, we constructe d a beta-galactosidase reporter gene system in human colon cancer DLD-1 cel ls, and measured COX-2 promoter-dependent transcriptional activity in the c ells. Interferon gamma suppressed this COX-2 promoter activity, while 12-O- tetradecanoylphorbol-13-acetate and transforming growth factor alpha (TGF a lpha) exerted enhancing effects. We then tested the influence of 14 candida te cancer chemopreventive compounds on COX-2 promoter activity. Chemopreven tive agents such as quercetin? kaempferol, genistein, resveratrol and resor cinol, all having a common resorcin moiety, were found to effectively suppr ess the COX-2 promoter activity with and without TGF alpha-stimulation in D LD-1 cells. Since all these compounds have a resorcin moiety as a common st ructure, a resorcin-type structure may play an active role in the inhibitio n of COX-2 expression in colon cancer cells.