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.
Expression of c-jun protein (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). Treatment of 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-1 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 mumol 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 mumol 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.(ABSTRACT TRUNCATED AT 400 WORDS)
Lu
Y P
YP
Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers-State University of New Jersey, Piscataway 08855.
Chang
R L
RL
Lou
Y R
YR
Huang
M T
MT
Newmark
H L
HL
Reuhl
K R
KR
Conney
A H
AH
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003043:Cocarcinogenesis; D003474:Curcumin / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006965:Hyperplasia; D051379:Mice; D008812:Mice, Hairless; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis*; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000096:biosynthesis*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects; D012878:Skin Neoplasms / Q000139:chemically induced; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014466:Ultraviolet Rays
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate