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

Int J Cancer. 2006 Aug 15;119(4):757-64. doi: 10.1002/ijc.21932.

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) (IC50 = 2-5 microM) and arrested cells in G1 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 microM), 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 microM). The data suggest that curcumin may execute its anticancer activity primarily by blocking mTOR-mediated signaling pathways in the tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Curcumin / pharmacology*
  • G1 Phase / drug effects
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Phosphoproteins / metabolism
  • Phosphorylation / drug effects
  • Phytotherapy
  • Protein Kinases / metabolism*
  • Resting Phase, Cell Cycle / drug effects
  • Rhabdomyosarcoma / drug therapy*
  • Rhabdomyosarcoma / metabolism*
  • Rhabdomyosarcoma / pathology
  • Ribosomal Protein S6 Kinases / metabolism
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Phosphoproteins
  • Tumor Suppressor Protein p53
  • Insulin-Like Growth Factor I
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases
  • Curcumin