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.

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.

• Authors: Rieko Yamauchi, Kaori Sasaki, Kenichi Yoshida
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 23 Issue 5 Pg. 834-9 (Aug 2009) ISSN: 1879-3177 [Electronic] England
• PMID: 19406223 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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