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Curcumin inhibits the mammalian target of rapamycin‐mediated signaling pathways in cancer cells
Author(s) -
Beevers Christopher S.,
Li Fengjun,
Liu Lei,
Huang Shile
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21932
Subject(s) - curcumin , pi3k/akt/mtor pathway , protein kinase b , p70 s6 kinase 1 , microbiology and biotechnology , biology , phosphorylation , signal transduction , cancer cell , cell cycle , apoptosis , cancer research , chemistry , biochemistry , cancer , genetics
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.