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.