Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells

Curcumin (diferuloylmethane), a polyphenol natural product of the plant Curcuma longa, is undergoing early clinical trials as a novel anticancer agent. However, the anticancer mechanism of curcumin remains to be elucidated. Here we show that curcumin inhibited growth of rhabdomyosarcoma cells (Rh1 and Rh30) (IC50 = 2-5 mu M) and arrested cells in G(1) phase of the cell cycle. Curcumin also induced apoptosis and inhibited the basal or type I insulin-like growth factor-induced motility of the cells. At physiological concentrations (similar to 2.5 mu M). curcumin rapidly inhibited phosphorylation of the mammalian target of rapamycin (mTOR) and kits downstream effector molecules. p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). in a panel of cell lines (Rh1, Rh30, DU145. MCF-7 and Hela). Curcumin also inhibited phosphorylation of Akt in the cells. but only at high concentrations (> 40 mu M). The data suggest that curcumin may execute its anticancer activity primarily by blocking mTOR-mediated signaling pathways in the tumor cells. (c) 2006 Wiley-Liss, Inc.