The effect of 12-O-tetradecanoylphorbol-13-acetate-induced COX-2 expression by 3,3'-Diindolylmethane (DIM) on Human Mammary Epithelial Cells

초록

3,3'-Diindolylmethane (DIM) is a major in vivo derivative of the putative anticancer agent indole-3-carbinol, which is present in cruciferous vegetables and has been reported to have anti-carcinogenic properties. An abnormally elevated level of cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of carcinogenesis. To investigate the mechanism by which DIM exhibits anti-carcinogenic effects, we investigated the effects of DIM on COX-2 expression in MCF-10A human mammary epithelial cells treated with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). DIM inhibited TPA-induced COX-2 expression and suppressed the synthesis of prostaglandin E2, one of the major products of COX-2. Nuclear factor-kappa B (NF-κB) is a transcription factor known to play a role in regulation of COX-2 expression. Treatment of MCF-10A cells with TPA increased nuclear translocation of phospho-p65, with the maximal levels being reached at 1 hour, while DIM inhibited the TPA-induced nuclear translocation of phospho-p65. Overall, we demonstrated that DIM suppresses phorbol ester-induced PGE2 production and COX-2 expression in MCF-10A cells. The reduction in COX-2 levels by DIM maybe mediated through inhibition of NF-κB signaling.

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