Chapter 20
Molecular Mechanism of Action of Curcumin Inhibition of 12-O-Tetradecanoylphorbol-13-acetate-Induced Responses Associated with Tumor Promotion
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J. K. L i n , T. S. Huang, C. A. Shih, and J. Y. Liu Institute of Biochemistry, College of Medicine, National Taiwan University, Number 1, Section 1, Jen-ai Road, Taipei, Taiwan, Republic of China
Curcumin is a potent inhibitor of tumor promotion by phorbol esters (Huang, M-T. et al., 1988). Our recent studies on the molecular mechanism of this inhibition have demonstrated that suppression of c-Jun/AP-1 activation by curcumin is observed in mouse fibroblast cells (Huang, T. S. et al., 1991). The functional activation of the transcription factor c-Jun/AP-1 is believed to play an important role in signal transduction of TPA-induced tumor promotion. Inhibition of c-Jun/AP-1 binding to its cognate motif by curcumin may be responsible for the inhibition of c-Jun/AP-1 mediated gene expression. The TPA-induced increase of protein kinase C in fibroblast cells is suppressed by curcumin. Furthermore, TPA-induced formation of 8-hydroxydeoxyguanosine in cellular D N A is significantly inhibited by curcumin. It appears that the processes of TPA-induced tumor promotion can be suppressed by curcumin through several biochemical pathways at different levels of genetic information.
Epidemiological investigations have demonstrated that environmental factors including dietary substances play a major role in the causation of cancer (1,2). Some dietary constituents have also received considerable attention in the chemoprevention of carcinogenesis (3,4). Many plant phenolics and carotenoids have been demonstrated to be effective blocking agents against chemical carcinogenesis (4-6). Curcumin is a typical plant phenolic and coloring matter from roots of Curcuma longa Linn., Curcuma aromatica Salisb., and Curcuma zedoaria Berg., Zingiberaceae. It has been widely used as a spice and coloring agent in curry, mustard and other foods. Curcumin has a wide range of biological and pharmacological activities including anti-thrombotic effect (1), antioxidant properties (8), antimutagenic effects in vitro (9), and in smokers (10), hypocholesterolemic effects in rats (11), and finally hypoglycemic effects in man (12). Recently, the inhibitory effects of curcumin and its structurally related compounds on chemical carcinogenesis in culture (13) and in mouse skin (14) have been investigated.
0097-6156/94/0547-0196$06.00/0 © 1994 American Chemical Society
In Food Phytochemicals for Cancer Prevention II; Ho, C., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1994.
20. LIN ET AL.
Molecular Mechanism of Action of Curcumin
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Effect of Curcumin on the Multiple Steps of Carcinogenesis Carcinogenesis is a multiple step process that can be divided into initiation, promotion and progression (15,16). Curcumin inhibits tumor initiation by 7,12-dimethylbenz[
