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.