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-tetradecanoylphor bol-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 lay er of epidermis and the muscle layer of dermis. Immunocytolochemical examin ation showed that pretreatment of 1 mu mol crocetin repressed the TPA-induc ed epidermal hyperplasia and the expressions of c-Jun, c-Fos and c-Myc to t he extent of 47, 44 and 45% respectively. Crocetin of 3.0 mu mol 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 indica te that crocetin suppresses the TPA-induced skin carcinogenesis maybe via i ts antioxidant property which, in turn, leads to a reduction in the TPA-ind uced expressions of c-Jun, c-Fos and c-Myc in mouse epidermis.