INHIBITION OF 12-O-TETRADECANOYLPHORBOL-13-ACETATE-CAUSED TUMOR PROMOTION IN BENZO[A]PYRENE-INITIATED CD-1 MOUSE SKIN BY GENIPOSIDE

The effects of topical application of geniposide on 12-o-tetradecanoyl phorbol-13-acetate (TPA)-induced promotion of skin tumors, hyperplasia , ornithine decarboxylase (ODC) and inflammation were evaluated in fem ale CD-1 mice. Topical application of geniposide (0.2 or 1.0 mu mol) w ith TPA (15 nmol) twice weekly for 20 weeks to mice previously initiat ed with benzo[a]pyrene (B[a]P) inhibited the number of TPA-induced tum or per mouse by 84 or 89%, respectively. Pre-application of the same a mount of geniposide also afforded significant protection against TPA-i nduced hyperplasia in the ear skin. Topical application of geniposide inhibited tumor promoter-caused induction of epidermal ODC activity by TPA (5 nmol). The topical application of geniposide (0.2 or 1.0 mu mo l) inhibited TPA-induced edema of mouse ears by 41 or 43%, respectivel y. Pretreatment of mouse skin with various amounts of geniposide cause d inhibition of hydrogen peroxide (H2O2) and myeloperoxidase (MPO) for mation by TPA. These results indicate that geniposide possesses potent ial as a cancer chemopreventive agent against tumor promotiom.