Inhibitory effects of curcumin on tumor initiation by benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene.
The effects of topical administration of curcumin on the formation of benzo[a]pyrene (B[a]P)-DNA adducts and the tumorigenic activities of B[a]P and 7,12-dimethylbenz[a]anthracene (DMBA) in epidermis were evaluated in female CD-1 mice. Topical application of 3 or 10 mumol curcumin 5 min prior to the application of 20 nmol [3H]B[a]P inhibited the formation of [3H]B[a]P-DNA adducts in epidermis by 39 or 61% respectively. In a two-stage skin tumorigenesis model, topical application of 20 nmol B[a]P to the backs of mice once weekly for 10 weeks followed a week later by promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks resulted in the formation of 7.1 skin tumors per mouse, and 100% of the mice had tumors. In a parallel group of mice, in which the animals were treated with 3 or 10 mumol curcumin 5 min prior to each application of B[a]P, the number of tumors per mouse was decreased by 58 or 62% respectively. The percentage of tumor-bearing mice was decreased by 18-25%. In an additional study, topical application of 3 or 10 mumol curcumin 5 min prior to each application of 2 nmol DMBA once weekly for 10 weeks followed a week later by promotion with 15 nmol TPA twice weekly for 15 weeks decreased the number of tumors per mouse by 37 or 41% respectively.
Huang
M T
MT
Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers University, Piscataway, NJ 08855-0789.
Wang
Z Y
ZY
Georgiadis
C A
CA
Laskin
J D
JD
Conney
A H
AH
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000287:Administration, Topical; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004336:Drug Antagonism; D005260:Female; D051379:Mice; D012878:Skin Neoplasms / Q000139:chemically induced*
D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D003474:Curcumin