Effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate- and ultraviolet B light-induced expression of c-Jun and c-Fos in JB6 cells and in mouse epidermis

• Published in: Carcinogenesis (New York) 1994-10, Vol.15 (10), p.2363-2370
• Main Authors: Lu, Yao-ping, Chang, Richard L., Lou, You-rong, Huang, Mou-Tuan, Newmark, Harold L., Reuhl, Kenneth R., Conney, Allan H.
• Format: Article
• Language: English
• Subjects: Animals; Cell Division - drug effects; Cell Transformation, Neoplastic; Cells, Cultured; Cocarcinogenesis; Curcumin - pharmacology; Drug Interactions; Female; Gene Expression Regulation - drug effects; Hyperplasia; Mice; Mice, Hairless; Proto-Oncogene Proteins c-fos - analysis; Proto-Oncogene Proteins c-fos - biosynthesis; Proto-Oncogene Proteins c-jun - analysis; Proto-Oncogene Proteins c-jun - biosynthesis; Skin - drug effects; Skin - metabolism; Skin - radiation effects; Skin Neoplasms - chemically induced; Tetradecanoylphorbol Acetate - pharmacology; Ultraviolet Rays
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/15.10.2363

Expression of c-jun was observed in normally Proliferating JB6 cells but not in confluent cells. Reduction of the serum concentration from 5% to 2% in the cell culture medium caused JB6 cells to enter a quiescent non-proliferating state and down-regulated the expression of c-Jun. Treatment of quiescent JB6 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) (10 ng/ml) for 24 h markedly stimulated the formation of c-Jun and caused morphological changes. Treatment of JB6 cells with TPA for 48 h resulted in transformed foci with mixed cell populations. Although some cells in these foci expressed high levels of c-Jun, many other cells did not. The increased expression of c-Jun and morphological changes observed at 24 h after treatment of JB6 cells with TPA (10 ng/ml) was inhibited by curcumin (10 nmol/ml). Treatmentof JB6 cells with 2.5, 5 or 10 nmol curcumin/ml inhibited the formation of TPA-induced anchorage-independent colonies that grow in soft agar by 31%, 43% and 77%, respectively. Although inhibition of cell proliferation was not observed with 2.5 nmol curcumin/ml, higher concentrations did inhibit cell proliferation. Topical application of 5 nmol TPA to the backs of CD-I mice once a day for 5 days caused epidermal hyperplasia and the levels of c-Jun were increased in the suprabasal layer of the epidermis and in the muscle layer of the dermis. This treatment also increased c-fos protein (c-Fos) expression in the muscle layer, but there was little or no increase in the expression of c-Fos in the basal or suprabasal layer of the epidermis. Topical application of 10 μmol curcumin together with 5 nmol TPA once a day for 5 days strongly inhibited TPA-induced epidermal hyperplasia and c-Jun and c-Fos expression. A single application of 180 mJ/cm2 of ultraviolet B light (UVB) to the backs of SKH-1 mice caused epidermal hyperplasia and expression of c-Fos and c-Jun in the muscle layer of the dermis and of c-Fos in the suprabasal layer of the epidermis. Maximum effects were observed at 6 days after UVB exposure. Application of 10 μmol curcumin to mouse skin twice a day for 5 days immediately after UVB exposure had only a small/variable inhibitory effect on UVB-induced increases in the expression of c-Fos and c-Jun and on epidermal hyperplasia. These data suggest that induction of hyperplasia and c-Jun and c-Fos expression in mouse skin by TPA and UVB may involve different pathways and that inhibition of TPA-induced skin tumorigenesis by curcumin may be associa