Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate.
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.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D002726:Chlorogenic Acid / Q000494:pharmacology*; D002934:Cinnamates / Q000494:pharmacology*; D003373:Coumaric Acids / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology* / Q000633:toxicity; D004247:DNA / Q000096:biosynthesis; D004487:Edema / Q000517:prevention & control; D005260:Female; D051379:Mice; D009955:Ornithine Decarboxylase / Q000032:analysis; D012867:Skin / Q000201:enzymology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate
D001095:Arachidonic Acids; D002109:Caffeic Acids; D002396:Catechols; D002934:Cinnamates; D003373:Coumaric Acids; D016718:Arachidonic Acid; D002726:Chlorogenic Acid; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; C004999:ferulic acid; D009955:Ornithine Decarboxylase; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate; C040048:caffeic acid