Epigallocatechin gallate inhibits the proliferation and induces apoptosis of multiple myeloma cells via inactivating EZH2

Eur Rev Med Pharmacol Sci. 2018 Apr;22(7):2093-2098. doi: 10.26355/eurrev_201804_14742.

Abstract

Objective: Epigallocatechin gallate (EGCG), the major chemical constituent of green tea, exhibits remarkable anti-tumor effect properties. In the present work, we aim to explore the effect and underlying mechanism of EGCG on multiple myeloma (MM) cells.

Materials and methods: The effects of EGCG on MM cells proliferation and apoptosis were determined by CCK-8 assay and flow cytometry assay. The siRNAs were used to inhibit endogenous expression of EZH2. Enforced expression of EZH2 in U266 cells was accomplished by transfecting EZH2 plasmid.

Results: EGCG suppressed proliferation and induced apoptosis in U266 cells, which accompanied by EZH2 inhibition. Moreover, we revealed that enforced expression of EZH2 increased MM cells proliferation and reduced cell apoptosis, whereas EGCG partially reversed the effects of EZH2 on MM cells progression. In addition, qRT-PCR and Western blot showed that EZH2 overexpression increased Bcl-2 expression, and decreased BAX, BAK1 and cytochrome c expression in U266 cells exposed to EGCG.

Conclusions: Our data showed that EGCG inhibited MM cells proliferation and induced apoptosis by targeting EZH2 and modulated mitochondrial apoptosis pathway, indicating EGCG might act as an adjuvant for chemotherapy of MM patients.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Catechin / analogs & derivatives*
  • Catechin / chemistry
  • Catechin / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Proliferation / physiology
  • Enhancer of Zeste Homolog 2 Protein / antagonists & inhibitors*
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Humans
  • Mitochondria / metabolism
  • Multiple Myeloma / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tea

Substances

  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Tea
  • Catechin
  • epigallocatechin gallate
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein