Anti-cancer effect of (-)-epigallocatechin-3-gallate (EGCG) in head and neck cancer through repression of transactivation and enhanced degradation of beta-catenin

Abstract

BACKGROUND AND PURPOSE: Aberrant expression of beta-catenin is highly associated with progression of various cancers including head and neck cancer (HNC). Green tea is most commonly used beverage in the world and one of the more bioactive compounds is the antioxidant epigallocatechin gallate (EGCG). This study was performed to investigate the mechanism by which EGCG inhibits the growth of HNC, focusing on the modulation of the expression and activity of beta-catenin. METHODS: In vitro effects of EGCG on the transcription, translation, or degradation of beta-catenin were investigated. Antitumor effects of EGCG in vivo were evaluated in a syngeneic mouse model and beta-catenin expression was checked in HNC patients' samples. RESULTS: beta-catenin expression was elevated in tumor samples of HNC patients. EGCG induced apoptosis in KB and FaDu cells through the suppression of beta-catenin signaling. Knockdown of beta-catenin using siRNA enhanced the proapoptotic activities of EGCG. EGCG decreased mRNA and transcriptional activity of beta-catenin in p53 wild-type KB cells. EGCG also enhanced the ubiquitination and proteasomal degradation of beta-catenin. The suppression of beta-catenin and consequent apoptosis were observed in response to EGCG treatment in a syngeneic mouse model. In conclusion, we report that EGCG inhibits beta-catenin expression through multiple mechanisms including decreased transcription and increased ubiquitin-mediated 26S proteasomal degradation. CONCLUSION: This study proposes a novel molecular rationale for antitumor activities of green tea in HNCs.