Resveratrol helps recovery from fatty liver and protects against hepatocellular carcinoma induced by hepatitis B virus X protein in a mouse model

Hsiu Ching Lin, Yi Fan Chen, Wen Hsin Hsu, Chu Wen Yang, Cheng Heng Kao, Ting Fen Tsai

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Resveratrol is a natural polyphenol that has beneficial effects across species and various disease models. Here, we investigate whether resveratrol is effective against hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) using HBVX protein (HBx) transgenic mice. We found that resveratrol (30 mg/kg/d) has a therapeutic effect on HBx-induced fatty liver and the early stages of liver damage. Resveratrol decreased intracellular reactive oxygen species and transiently stimulated hepatocyte proliferation. Interestingly, resveratrol inhibited LXRα and downregulated the expression of the lipogenic genes, Srebp1-c and PPARγ. The decrease in Srebp1-c seems to further downregulate the expression of its target genes, Acc and Fas. In addition, resveratrol stimulated the activity of Ampk and SirT1. Thus, resveratrol has a pleiotropic effect on HBx transgenic mice in terms of the downregulation of lipogenesis, the promotion of transient liver regeneration, and the stimulation of antioxidant activity. Furthermore, at the later precancerous stages, resveratrol delayed HBx-mediated hepatocarcinogenesis and reduced HCC incidence from 80% to 15%, a 5.3-fold reduction. Resveratrol should be considered as a potential chemopreventive agent for HBV-associated HCC.

Original languageEnglish
Pages (from-to)952-962
Number of pages11
JournalCancer Prevention Research
Volume5
Issue number7
DOIs
Publication statusPublished - Jul 2012
Externally publishedYes

Fingerprint

Fatty Liver
Hepatocellular Carcinoma
Down-Regulation
Hepatitis B virus
Transgenic Mice
Proteins
hepatitis B virus X protein
resveratrol
Lipogenesis
Peroxisome Proliferator-Activated Receptors
Liver Regeneration
Polyphenols
Therapeutic Uses
Hepatocytes
Reactive Oxygen Species
Antioxidants
Gene Expression
Liver
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Resveratrol helps recovery from fatty liver and protects against hepatocellular carcinoma induced by hepatitis B virus X protein in a mouse model. / Lin, Hsiu Ching; Chen, Yi Fan; Hsu, Wen Hsin; Yang, Chu Wen; Kao, Cheng Heng; Tsai, Ting Fen.

In: Cancer Prevention Research, Vol. 5, No. 7, 07.2012, p. 952-962.

Research output: Contribution to journalArticle

Lin, Hsiu Ching ; Chen, Yi Fan ; Hsu, Wen Hsin ; Yang, Chu Wen ; Kao, Cheng Heng ; Tsai, Ting Fen. / Resveratrol helps recovery from fatty liver and protects against hepatocellular carcinoma induced by hepatitis B virus X protein in a mouse model. In: Cancer Prevention Research. 2012 ; Vol. 5, No. 7. pp. 952-962.
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