MOLECULAR MECHANISM OF ACTION OF CURCUMIN INHIBITION OF 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED RESPONSES ASSOCIATED WITH TUMOR PROMOTION

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 DNA 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.