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

Abstract

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) (IC 50 = 2–5 μM) 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 (˜2.5 μM), curcumin rapidly inhibited phosphorylation of the mammalian target of rapamycin (mTOR) and its 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 μM). The data suggest that curcumin may execute its anticancer activity primarily by blocking mTOR‐mediated signaling pathways in the tumor cells. © 2006 Wiley‐Liss, Inc.