Implication of Akt, ERK1/2 and alternative p38MAPK signalling pathways in human colon cancer cell apoptosis induced by green tea EGCG

Food Chem Toxicol. 2015 Oct:84:125-32. doi: 10.1016/j.fct.2015.08.017. Epub 2015 Aug 21.

Abstract

We investigated apoptosis induced by the green tea component the epigallocatechin-3-gallate (EGCG) and the pathways underlying its activity in a colon cancer cell line. A complete understanding of the mechanism(s) and molecules targeted by green tea polyphenols could be useful in developing novel therapeutic approaches for cancer treatment. EGCG, which is the major polyphenol in green tea, has cytotoxic effects and induced cell death in HT-29 cell death. In this study, we evaluated the effect EGCG on mitogen-activated protein kinase (MAPK) and Akt pathways. EGCG treatment increased phospho-ERK1/2, -JNK1/2 and -p38α, -p38γ and -p38δ, as well as phospho-Akt levels. Using a combination of kinase inhibitors, we found that EGCG-induced cell death is partially blocked by inhibiting Akt, ERK1/2 or alternative p38MAPK activity. Our data suggest that these kinase pathways are involved in the anti-cancer effects of EGCG and indicate potential use of this compound as chemotherapeutic agent for colon cancer treatment.

Keywords: Akt; Apoptosis; Colon cancer; EGCG; ERK; p38γ/p38δ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / metabolism*
  • Antioxidants / metabolism*
  • Apoptosis* / drug effects
  • Catechin / analogs & derivatives*
  • Catechin / metabolism
  • Cell Line, Tumor
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / prevention & control
  • Food Handling
  • HEK293 Cells
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • MAP Kinase Signaling System* / drug effects
  • Osmolar Concentration
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Processing, Post-Translational / drug effects
  • Proto-Oncogene Proteins c-akt / agonists*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • RNA, Small Interfering
  • Tea / chemistry
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / chemistry
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anticarcinogenic Agents
  • Antioxidants
  • Isoenzymes
  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • Tea
  • Catechin
  • epigallocatechin gallate
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases