Anti-cancer effect of (-)-epigallocatechin-3-gallate (EGCG) in head and neck cancer through repression of transactivation and enhanced degradation ofβ-catenin.
Phytomedicine. 2016 Nov 15 ;23(12):1344-1355. Epub 2016 Aug 19. PMID: 27765354
Yoo Seob Shin
BACKGROUND AND PURPOSE: Aberrant expression ofβ-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 β-catenin.
METHODS: In vitro effects of EGCG on the transcription, translation, or degradation ofβ-catenin were investigated. Antitumor effects of EGCG in vivo were evaluated in a syngeneic mouse model and β-catenin expression was checked in HNC patients' samples.
RESULTS: β-catenin expression was elevated in tumor samples of HNC patients. EGCG induced apoptosis in KB and FaDu cells through the suppression of β-catenin signaling. Knockdown of β-catenin using siRNA enhanced the proapoptotic activities of EGCG. EGCG decreased mRNA and transcriptional activity of β-catenin in p53 wild-type KB cells. EGCG also enhanced the ubiquitination and proteasomal degradation of β-catenin. The suppression of β-catenin and consequent apoptosis were observed in response to EGCG treatment in a syngeneic mouse model. In conclusion, we report that EGCG inhibits β-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.