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HORMONES AND SIGNALING

Activation of PPAR by curcumin inhibits Moser cell growth and mediates suppression of gene expression of cyclin D1 and EGFR

Departments of ¹Pathology and ²Cellular Biology and Anatomy, Louisiana State University Health Sciences Center in Shreveport, Shreveport, Louisiana

Submitted 6 May 2004 ; accepted in final form 9 October 2004

Colorectal cancer is a leading cause of cancer-related morbidity and mortality in the United States. Curcumin, the yellow pigment in turmeric, possesses inhibitory effects on growth of a variety of tumor cells by reducing cell proliferation and inducing apoptosis. Effects of the peroxisome proliferator-activated receptor- (PPAR) on stimulating cell differentiation and on inducing cell cycle arrest have attracted attention from the perspective of treatment and prevention of cancer. The aim of this study was to elucidate the mechanisms by which curcumin inhibits colon cancer cell growth. In the present report, we observed that curcumin, in a dose-dependent manner, inhibited the growth of Moser cells, a human colon cancer-derived cell line, and stimulated the trans-activating activity of PPAR. Further studies demonstrated that activation of PPAR was required for curcumin to inhibit Moser cell growth. Activation of PPAR mediated curcumin suppression of the expression of cyclin D1, a critical protein in the cell cycle, in Moser cells. In addition, curcumin blocked EGF signaling by inhibiting EGF receptor (EGFR) tyrosine phosphorylation and suppressing the gene expression of EGFR mediated by activation of PPAR. In addition to curcumin reduction of the level of phosphorylated PPAR, inhibition of cyclin D1 expression played a major and significant role in curcumin stimulation of PPAR activity in Moser cells. Taken together, our results demonstrated for the first time that curcumin activation of PPAR inhibited Moser cell growth and mediated the suppression of the gene expression of cyclin D1 and EGFR. These results provided a novel insight into the roles and mechanisms of curcumin in inhibition of colon cancer cell growth and potential therapeutic strategies for treatment of colon cancer.

colon cancer; receptors; phytochemicals; gene expression; chemoprevention

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