Suppression of the TPA-induced expression of nuclear-protooncogenes in mouse epidermis by crocetin via antioxidant activity

Crocetin, a major component of the fruit of Gardenia jasminoides Ellis, was investigated for its anti-tumor promoting effect on 12-O-tetradecanoylphorbol-13-acetate-promoted mouse skin carcinogenesis. Topical application of 5 nmol TPA to CD-1 mice once daily for 5 days caused epidermal hyperplasia, and increases in the levels of c-Fos, c-Jun and c-Myc in the suprabasal layer of epidermis and the muscle layer of dermis. Immunocytolochemical examination showed that pretreatment of 1 μmol crocetin repressed the TPA-induced epidermal hyperplasia and the expressions of c-Jun, c-Fos and c-Myc to the extent of 47, 44 and 45% respectively. Crocetin of 3.0 μmol exhibited stronger inhibition on the induced hyperplasia and the oncoproteins levels (by 60, 53 and 55% respectively). Western blotting analysis confirmed this inhibitory effect of crocetin. Pretreatment of crocetin also repressed the TPA-induced H2O2 production and myeloperoxidase activity. These data indicate that crocetin suppresses the TPA-induced skin carcinogenesis maybe via its antioxidant property which, in turn, leads to a reduction in the TPA-induced expressions of c-Jun, c-Fos and c-Myc in mouse epidermis.