Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate

• Published in: Cancer research (Chicago, Ill.) Ill.), 1988-11, Vol.48 (21), p.5941-5946
• Main Authors: MOU-TUAN HUANG, SMART, R. C, CHING-QUO WONG, CONNEY, A. H
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Animals; Arachidonic Acid; Arachidonic Acids - metabolism; Biological and medical sciences; Caffeic Acids - pharmacology; Carcinogenesis, carcinogens and anticarcinogens; Catechols - pharmacology; Chemical agents; Chlorogenic Acid - pharmacology; Cinnamates - pharmacology; Coumaric Acids - pharmacology; Curcumin - pharmacology; Curcumin - toxicity; DNA - biosynthesis; Edema - prevention & control; Female; Medical sciences; Mice; Ornithine Decarboxylase - analysis; Skin - enzymology; Skin Neoplasms - chemically induced; Skin Neoplasms - prevention & control; Tetradecanoylphorbol Acetate; Tumors
• ISSN: 0008-5472; 1538-7445

The effects of topically applied curcumin, chlorogenic acid, caffeic acid, and ferulic acid on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal ornithine decarboxylase activity, epidermal DNA synthesis, and the promotion of skin tumors were evaluated in female CD-1 mice. Topical application of 0.5, 1, 3, or 10 mumol of curcumin inhibited by 31, 46, 84, or 98%, respectively, the induction of epidermal ornithine decarboxylase activity by 5 nmol of TPA. In an additional study, the topical application of 10 mumol of curcumin, chlorogenic acid, caffeic acid, or ferulic acid inhibited by 91, 25, 42, or 46%, respectively, the induction of ornithine decarboxylase activity by 5 nmol of TPA. The topical application of 10 mumol of curcumin together with 2 or 5 nmol of TPA inhibited the TPA-dependent stimulation of the incorporation of [3H]-thymidine into epidermal DNA by 49 or 29%, respectively, whereas lower doses of curcumin had little or no effect. Chlorogenic acid, caffeic acid, and ferulic acid were less effective than curcumin as inhibitors of the TPA-dependent stimulation of DNA synthesis. Topical application of 1, 3, or 10 mumol of curcumin together with 5 nmol of TPA twice weekly for 20 weeks to mice previously initiated with 7,12-dimethylbenz[a]anthracene inhibited the number of TPA-induced tumors per mouse by 39, 77, or 98%, respectively. Similar treatment of mice with 10 mumol of chlorogenic acid, caffeic acid, or ferulic acid together with 5 nmol of TPA inhibited the number of TPA-induced tumors per mouse by 60, 28, or 35%, respectively, and higher doses of the phenolic acids caused a more pronounced inhibition of tumor promotion. The possibility that curcumin could inhibit the action of arachidonic acid was evaluated by studying the effect of curcumin on arachidonic acid-induced edema of mouse ears. The topical application of 3 or 10 mumol of curcumin 30 min before the application of 1 mumol of arachidonic acid inhibited arachidonic acid-induced edema by 33 or 80%, respectively.