Chemopreventive activities of etodolac and oxyphenbutazone against mouse skin carcinogenesis.

Previous cancer chemoprevention studies have demonstrated that the non-steroidal anti-inflammatory drugs (NSAIDs) can be effective in suppressing the development of various human malignancies. Recently we identified the possible anti-tumor promoting potentials of 14 new NSAIDs in the Epstein-Barr virus early antigen activation assay induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). In this study we report the inhibition of 7,12-dimethylbenz (a) anthracene (DMBA) induced two-stage mouse skin carcinogenesis by etodolac (ETD), one of the most potent NSAIDs identified in our in vitro cancer chemopreventive screening of this group of drugs. Topical administration of ETD at a very low dose of 85 nmol showed a significant decrease in both tumor incidence and burden. This effect is also accompanied by a delay in the tumor latency period. Since ETD showed potent chemopreventive activity in both in vitro and in vivo studies, it warrants prompt consideration for trial in humans as a potential cancer chemopreventive agent. We also investigated oxyphenbutazone (OPB) another commonly used NSAID for its cancer chemopreventive effect on peroxynitrite (PN) induced-TPA promoted skin tumors in the mouse. Following tumor initiation with 390 nmol of PN, the skin tumor promotion with 1.7 nmol of TPA was significantly inhibited by oral administration of 0.0025% OPB. The results demonstrate that OPB is a potent cancer chemopreventive agent in the highly sensitive in vivo mouse test model we used.