INHIBITORY EFFECT OF SILYMARIN, AN ANTIHEPATOTOXIC FLAVONOID, ORE 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED EPIDERMAL ORNITHINE DECARBOXYLASE ACTIVITY AND MESSENGER-RNA IN SENCAR MICE

In recent years, considerable emphasis has been placed on identifying new cancer chemopreventive agents which could be useful for human populations. Silymarin, an anti-oxidant flavonoid isolated from artichoke, has been shown to possess siginificant activity against hepatotoxicity and other pharmacological and physiological disorders. Since many antioxidants inhibit tumor promotion, and because ornithine decarboxylase (ODC) is a well known biochemical marker of tumor promotion, we assessed the effect of skin application of silymarin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal ODC activity and ODC mRNA levels in SENCAR mice. Application of silymarin at doses of 0.5-18 mg (1-37 mu mol)/mouse prior to that of TPA (2.5 mu g) treatment resulted in significant inhibition of TPA-induced epidermal ODC activity in a dose- and time-dependent manner. Northern blot analysis revealed that topical application of silymarin at the dose of 2 mg/mouse resulted in almost complete inhibition of TPA-induced epidermal ODC mRNA. In other studies, silymarin also showed significant inhibition of epidermal ODC activity induced by several other tumor promoters, including free radical-generating compounds. Our data suggest that silymarin could be a useful anti-tumor promoting agent capable of ameliorating the tumor promoting effects of a wide range of tumor promoters.