title: Inhibitory effects of topical application of low doses of curcumin on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion and oxidized DNA bases in mouse epidermis.
abstract: The effects of topical applications of very low doses of curcumin (the major yellow pigment in turmeric and the Indian food curry) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidation of DNA bases in the epidermis and on tumor promotion in mouse skin were investigated. CD-1 mice were treated topically with 200 nmol of 7,12-dimethylbenz[a]anthracene followed one week later by 5 nmol of TPA alone or together with 1, 10, 100 or 3000 nmol of curcumin twice a week for 20 weeks. Curcumin-mediated effects on TPA-induced formation of the oxidized DNA base 5-hydroxymethyl-2'-deoxyuridine (HMdU) and tumor formation were determined. All dose levels of curcumin inhibited the mean values of TPA-induced HMdU formation in epidermal DNA (62-77% inhibition), but only the two highest doses of curcumin strongly inhibited TPA-induced tumor promotion (62-79% inhibition of tumors per mouse and tumor volume per mouse). In a second experiment, topical application of 20 or 100 nmol (but not 10 nmol) of curcumin together with 5 nmol TPA twice a week for 18 weeks markedly inhibited TPA-induced tumor promotion. Curcumin had a strong inhibitory effect on DNA and RNA synthesis (IC50 = 0.5-1 microM) in cultured HeLa cells, but there was little or no effect on protein synthesis.
authors.affiliation: Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway 08855-0789, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Huang
authors.forename: W
authors.initials: W
authors.lastname: Ma
authors.forename: P
authors.initials: P
authors.lastname: Yen
authors.forename: J G
authors.initials: JG
authors.lastname: Xie
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.forename: K
authors.initials: K
authors.lastname: Frenkel
authors.forename: D
authors.initials: D
authors.lastname: Grunberger
authors.forename: A H
authors.initials: AH
authors.lastname: Conney
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000287:Administration, Topical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control; D010084:Oxidation-Reduction; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate