Inhibition of glycoprotein synthesis in the endoplasmic reticulum as a novel anticancer mechanism of (-)-epigallocatechin-3-gallate

Laura Konta, Péter Száraz, Judit É Magyar, Katalin Révész, Gábor Bánhegyi, József Mandl, Miklós Csala

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

(-)-Epigallocatechin-3-gallate (EGCG) has been found to trigger the unfolded protein response (UPR) likely due to the inhibition of glucosidase II, a key enzyme of glycoprotein processing and quality control in the endoplasmic reticulum (ER). These findings strongly suggest that EGCG interferes with glycoprotein maturation and sorting in the ER. This hypothesis was tested in SK-Mel28 human melanoma cells by assessing the effect of EGCG and deoxynojirimycin (DNJ) on the synthesis of two endogenous glycoproteins. Both tyrosinase and vascular endothelial growth factor (VEGF) protein levels were remarkably reduced despite unaltered mRNA expression in EGCG- or DNJ-treated cells compared to control. The hindrance of tyrosinase and VEGF protein synthesis could be prevented by proteasome inhibitor, lactacystine. Collectively, our results support that glucosidase II inhibitor EGCG interferes with protein processing and quality control in the ER, which diverts tyrosinase, VEGF, and likely other glycoproteins towards proteasomal degradation. This mechanism provides a novel therapeutic approach in dermatology and might play an important role in the antitumor effect or hepatotoxicity of EGCG.

Original languageEnglish
Pages (from-to)468-476
Number of pages9
JournalBioFactors
Volume37
Issue number6
DOIs
Publication statusPublished - Nov 1 2011

Keywords

  • ERAD
  • Glucosidase II
  • Proteasome
  • Tyrosinase
  • VEGF

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Clinical Biochemistry

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