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Tumor Biology

, Volume 35, Issue 1, pp 205–212 | Cite as

A potential antitumor ellagitannin, davidiin, inhibited hepatocellular tumor growth by targeting EZH2

  • Yan Wang
  • Jingyi Ma
  • Sheung Ching Chow
  • Chi Han Li
  • Zhangang Xiao
  • Ru Feng
  • Jie Fu
  • Yangchao Chen
Research Article

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is the third most common cause of cancer-related deaths. Currently available treatment options for HCC patients are scarce resulting in an urgent need to develop a novel effective cure. Polygonum capitatum is a medicinal herb which has been used to treat inflammatory diseases in Miao nationality of China. We recently isolated a pure compound davidiin from P. capitatum extract. Four HCC cell lines were treated with davidiin. Cell viability was recorded by MTT assay. siRNAs targeting enhancer of zeste homolog 2 (EZH2) were applied to modulate the expression of EZH2. Established xenograft mice models of HCC were applied to evaluate the in vivo anticancer activity of davidiin. We investigated the anticancer activity and the underlying mechanism of davidiin. The compound inhibited HCC cell growth and also suppressed tumor growth in xenografted HCC mouse. Such inhibition was facilitated by specifically downregulation on EZH2. The compound possesses anticancer activity both in vitro and in vivo which warrants further clinical investigation as a potential anti-HCC agent.

Keywords

Hepatocellular carcinoma Enhancer of zeste homolog 2 Traditional Chinese medicine Anticancer drug 

Abbreviations

Bmi-1

B lymphoma Mo-MLV insertion region 1 homolog

CBX

Chromobox protein homologue

DMSO

Dimethylsulfoxide

EDTA

Ethylenediaminetetraacetic acid

EED

Embryonic ectoderm development

EZH2

Enhancer of zeste homolog 2

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

HCC

Hepatocellular carcinoma

HRP

Horseradish peroxidase

H3K27me3

Histone H3 trimethylated on lysine 27

MG132

N-(benzyloxycarbonyl)leucinylleucinylleucinal Z-Leu-Leu-Leu-al

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PARP

Poly ADP ribose polymerase

PcG protein

Polycomb group protein

PCR

Polymerase chain reaction

PH

Polyhomeotic

PI

propidium iodide

PRC

Polycomb repressor complex

PVDF

Polyvinylidene difluoride

RBAP48

Retinoblastoma-binding protein p48

SFN

Sulforaphane

SUZ12

Suppressor of zeste 12

TCM

Traditional Chinese medicine

TUNEL

Terminal deoxynucleotidyl transferase dUTP nick end labeling

Notes

Acknowledgments

This work was supported by grants from the Research Grants Council General Research Fund of Hong Kong [CUHK462109 and CUHK462211], National Natural Science Foundation of China [81101888], Shenzhen Basic Research Program [JC201105201092A], Direct Grant from CUHK to YC, NSFC grant [81072611], National Science and Technology Special Projects [2012ZX09301002-006], and the Special Fund of Chinese Central Government for Basic Scientific Research Operations [2012CHX08] to YW.

Conflicts of interest

None

Supplementary material

13277_2013_1025_MOESM1_ESM.pdf (351 kb)
Open Resource Statistical analysis of western blots shown in Figs. 1e and 2a, c. (a) Reduced caspase 3 level and increase in both PARP and caspase 3 cleavages were detected in both Hep3B and Bel7404 cells treated with davidiin. (b) Reduced the levels of EZH2, H3K27me3, and cyclin D1 were observed when Hep3B and Bel7404 were treated with davidiin. (c) Davidiin-induced EZH2 reduction was reversed by MG132, when davidiin-treated HCC cells were co-treated with a proteasome inhibitor, MG132. Transcript levels between groups were considered as significantly different when p < 0.05 (*p < 0.05, **p < 0.01 vs. control, n = 3) (PDF 351 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Yan Wang
    • 1
  • Jingyi Ma
    • 1
  • Sheung Ching Chow
    • 2
  • Chi Han Li
    • 2
  • Zhangang Xiao
    • 2
  • Ru Feng
    • 1
  • Jie Fu
    • 1
  • Yangchao Chen
    • 2
    • 3
  1. 1.State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia MedicaChinese Academy of Medical SciencesBeijingChina
  2. 2.School of Biomedical Sciences, Faculty of MedicineThe Chinese University of Hong KongShatinHong Kong
  3. 3.Shenzhen Research InstituteThe Chinese University of Hong KongShenzhenChina

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