Identification of epigallocatechin-3-gallate in green tea polyphenols as a potent inducer of p53-dependent apoptosis in the human lung cancer cell line A549

Toxicol In Vitro. 2009 Aug;23(5):834-9. doi: 10.1016/j.tiv.2009.04.011. Epub 2009 May 3.

Abstract

The effects of green tea polyphenols on cultured cancer cells have been well characterized, especially the effects of epigallocatechin-3-gallate (EGCg), since EGCg suppresses oncogenic signaling pathways and induces cell cycle arrest or apoptosis by regulating cell cycle-associated proteins. In the present study, we attempted to identify signaling pathways or target molecules regulated by each of or a mixture of green tea polyphenols, including epicatechin (EC), epicatechin-3-gallate (ECg), epigallocatechin (EGC), and EGCg, in the human lung cancer cell line A549. ECg, EGC, and a catechin mixture, in addition to EGCg, significantly decreased cell viability. In contrast, caspase 3/7 activity, an apoptosis indicator, was specifically induced by EGCg. By conducting a series of luciferase-based reporter assays, we revealed that the catechin mixture only up-regulates the p53 reporter. EGCg was a more potent inducer of p53-dependent transcription, and this induction was further supported by the induced level of p53 protein. RNA interference (RNAi)-mediated p53 knockdown completely abolished EGCg-induced apoptosis. Finally, a proteome and western blot analysis using approximately 70 different antibodies failed to detect up-regulated proteins in catechin mixture-treated A549 cells. Taken together, these results indicate that EGCg, among several green tea polyphenols, is a potent apoptosis inducer that functions exclusively through a p53-dependent pathway in A549 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism
  • Caspase 7 / drug effects
  • Caspase 7 / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / isolation & purification
  • Catechin / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Humans
  • Luciferases / metabolism
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Phenols / isolation & purification
  • Phenols / pharmacology*
  • Polyphenols
  • Signal Transduction / drug effects
  • Tea / chemistry*
  • Tumor Suppressor Protein p53 / drug effects
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Flavonoids
  • Phenols
  • Polyphenols
  • Tea
  • Tumor Suppressor Protein p53
  • Catechin
  • epigallocatechin gallate
  • Luciferases
  • Caspase 3
  • Caspase 7