Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway

Cancer Lett. 2007 Mar 8;247(1):115-21. doi: 10.1016/j.canlet.2006.03.030. Epub 2006 Jun 21.


EGCG [(-)epigallocatechin-3-gallate], a green tea-derived polyphenol, has been shown to suppress cancer cell proliferation, and interfere with the several signaling pathways and induce apoptosis. Practically, there is emerging evidence that EGCG has a potential to increase the efficacy of chemotherapy in patients. We hypothesized that EGCG may exert cell cytotoxicity through modulating AMPK (AMP-activated protein kinase) followed by the decrease in COX-2 expression. EGCG treatment to colon cancer cells resulted in a strong activation of AMPK and an inhibition of COX-2 expression. The decreased COX-2 expression as well as prostaglandin E(2) secretion by EGCG was completely abolished by inhibiting AMPK by an AMPK inhibitor, Compound C. Also, the activation of AMPK was accompanied with the reduction of VEGF (vascular endothelial growth factor) and glucose transporter, Glut-1 in EGCG-treated cancer cells. These findings support the regulatory role of AMPK in COX-2 expression in EGCG-treated cancer cells. Furthermore, we have found that reactive oxygen species (ROS) is an upstream signal of AMPK, and the combined treatment of EGCG and chemotherapeutic agents, 5-FU or Etoposide, exert a novel therapeutic effect on chemo-resistant colon cancer cells. AMPK, a molecule of newly defined cancer target, was shown to control COX-2 in EGCG-treated colon cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis / drug effects
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Colonic Neoplasms / metabolism*
  • Cyclooxygenase 2 / physiology*
  • Gene Expression Regulation, Neoplastic
  • HT29 Cells
  • Humans
  • Membrane Proteins / physiology*
  • Protein Kinases / physiology*
  • Pyrazoles / pharmacology
  • Pyrimidines / pharmacology
  • Reactive Oxygen Species / analysis
  • Signal Transduction


  • Membrane Proteins
  • Pyrazoles
  • Pyrimidines
  • Reactive Oxygen Species
  • dorsomorphin
  • Catechin
  • epigallocatechin gallate
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Protein Kinases
  • AMP-activated protein kinase kinase