The effects of topical application of crocetin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin tumors, hyperplasia, hydrogen peroxide, ornithine decarboxylase (ODC) and inflammation were evaluated in female CD-1 mice. Topical application of crocetin (0.2 or 1.0 mumol) with TPA (15 nmol) twice weekly for 20 weeks to mice previously initiated with benzo[a]pyrene (B[a]P) inhibited the number of TPA-induced tumors per mouse by 69 and 81% respectively. Pre-application of the same amount of crocetin also afforded significant protection against TPA-induced hyperplasia in the ear skin. Topical application of crocetin inhibited tumor promoter-caused induction of epidermal ODC activity by TPA (5 nmol). The topical application of crocetin (0.2 or 1.0 mumol) inhibited TPA-induced edema of mouse ears by 76 and 87% respectively. Pretreatment of mouse skin with various amounts of crocetin caused inhibition of hydrogen peroxide and myeloperoxidase production by TPA. These results indicate that crocetin possesses potential as a cancer chemopreventive agent against tumor promotion.
