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Biofactors. 2014 Nov-Dec;40(6):586-95. doi: 10.1002/biof.1185. Epub 2014 Oct 29.

Green tea polyphenol EGCG suppresses Wnt/β-catenin signaling by promoting GSK-3β- and PP2A-independent β-catenin phosphorylation/degradation.

Author information

1
Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul, Republic of Korea.

Abstract

(-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been reported to inhibit the Wnt/β-catenin pathway, which is aberrantly up-regulated in colorectal cancers, but its precise mechanism of action remains unclear. Here, we used a sensitive cell-based system to demonstrate that EGCG suppresses β-catenin response transcription (CRT), activated by Wnt3a-conditioned medium (Wnt3a-CM), by promoting the degradation of intracellular β-catenin. EGCG induced β-catenin N-terminal phosphorylation at the Ser33/37 residues and subsequently promoted its degradation; however, this effect was not observed for oncogenic forms of β-catenin. Pharmacological inhibition or depletion of glycogen synthase kinase-3β (GSK-3β) did not abrogate the EGCG-mediated β-catenin degradation. EGCG did not affect the activity and expression of protein phosphatase 2A (PP2A). Consistently, the phosphorylation and degradation of β-catenin was found in adenomatous polyposis coli (APC) mutated colon cancer cells after EGCG treatment. EGCG repressed the expression of cyclin D1 and c-myc, which are β-catenin/T-cell factor-dependent genes, and inhibited the proliferation of colon cancer cells. Our findings suggest that EGCG exerts its cancer-preventive or anticancer activity against colon cancer cells by promoting the phosphorylation and proteasomal degradation of β-catenin through a mechanism independent of the GSK-3β and PP2A.

KEYWORDS:

(−)-epigallocatechin-3-gallate; Wnt/β-catenin signaling; colon cancer; phosphorylation; proteasomal degradation

PMID:
25352148
PMCID:
PMC4285564
DOI:
10.1002/biof.1185
[Indexed for MEDLINE]
Free PMC Article

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