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© 1993 Oxford University Press

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Inhibitory effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate-induced increase in ornithine decarboxylase mRNA in mouse epidermis

Yao-Ping Lu, Richard L.Chang, Mou-Tuan Huang and Allan H.Conney

Laboratory for Cancer Research, Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers, The State University of New Jersey Piscataway, NJ 08855–0789, USA

Application of 5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) to the skin of female CD-1 mice led to a rapid increase in the concentration of epidermal ornithine decarboxylase (ODC) mRNA from an undetectable level in control mice to a high maximum level at 4–5 h after TPA administration. The concentration of epidermal ODC mRNA then decreased rapidly during the next 5 h. The time course for TPA-induced increases in epidermal ODC enzyme activity paralleled very closely the time course for TPA-induced increases in ODC mRNA. Topical administration of 1, 3 or 10µmol curcumin together with 5 nmol TPA inhibited by 66, 81 and 91% respectively TPA-induced increases in epidermal ODC enzyme activity measured 5 h later. In a parallel study, TPA-induced increases in the concentration of epidermal ODC mRNA was inhibited by 54, 85 and 82% respectively. Intraperitoneal injection of 10 or 30 µmol curcumin 1h before topical application of 5 nmol TPA inhibited TPA-induced increases in epidermal ODC enzyme activity by 75 or 89% respectively. In a parallel study, the induction of epidermal ODC mRNA was inhibited by 53 and 65% respectively. The results indicate that curcumin inhibits TPA-induced increases in epidermal ODC enzyme activity by inhibiting the synthesis and/or enhancing the breakdown of ODC mRNA.


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