Chemoprevention of HBV-related hepatocellular carcinoma by the combined product of resveratrol and silymarin in transgenic mice

Authors

  • Wen-Chuan Hsieh National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan
  • Ching-Wen Yang Institute of Basic Medical Research, National Cheng Kung University Medical School, Tainan
  • Yi-Sheng Haung National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan
  • Ting-Wei Chao National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan
  • Tin-Fen Tsai Faculty of Life Sciences and Institute of Genetics, National Yang-Ming University, Taipei
  • Ih-Jen Su National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan

DOI:

https://doi.org/10.31989/ffhd.v3i9.41

Abstract

Background: Patients with chronic hepatitis B virus (HBV) infection are at a high risk to develop hepatocellular carcinoma (HCC). Recently, metabolic syndrome has been found to carry a risk for HCC development. Considering the limitation of chemotherapeutic drugs for HCCs, the development of chemopreventive agents for high risk chronic HBV carriers is urgently demanded. In this study, we used combined silymarin and resveratrol extract which have been shown to exhibit biologic effects on activating peroxisome proliferator activated receptors (PPAR) and inhibiting mTOR signaling in a transgenic mice model harboring HBV viral oncoproteins.

Methods: The transgenic mice model harboring HBx and pre-S2 mutant constructs which develop HCC was adopted. First, we in vitro tested the ideal combination dosages of the silymarin and resveratrol product, and then we fed the natural product to the transgenic mice. The chemopreventive effects on preventing the development of HCC were evaluated.

Results: MTT assay showed an enhanced effect of the combined silymarin and resveratrol product on the reduction of cell proliferation in two hepatoma cell lines, Huh-7 and Hep G2. In vitro reporter assay and Western blot analyses revealed that the combined product could activate PPAR/PGC-1α signaling and inhibit mTOR expression. In vivo, the combined products could significantly ameliorate fatty liver and reduce HCCs in transgenic mice harboring HBV oncoproteins.

Conclusions: The combined silymarin and resveratrol product exhibits a synergistic effect on the reduction of HCC development in transgenic mice model and may represent a potential agent for the prevention of HCC in high risk chronic HBV carriers.

Key words: HBV, HCC, Transgenic mice, Chemoprevention

Downloads

Published

2013-09-30

Issue

Vol. 3 No. 9 (2013): September 2013

Section

Research Articles

License

Any manuscripts or substantial parts of it, submitted to the journal must not be under consideration by or previously published in any other journal or citable form. Authors are required to ensure that no material submitted as part of a manuscript infringes existing copyrights or the rights of a third party. In submitting one's article in any form, the author has assigned the FFC publishing rights and has agreed to an automatic transfer of the copyright to the publisher. This is so that the FFC may create print option journals, for example, at the FFC’s discretion. If the author wishes to distribute their works by means outside of the FFC, for example within their community, they will have to place a request. 

 

Correspondence concerning articles published in Functional Foods in Health and Disease is encouraged. While derivative works (adaptations, extensions on the current work, etc.) are allowed, distribution of the modified material is not allowed without permission from the FFC.