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

Authors retain the copyright of their articles and grant the Functional Food Center (FFC) and its journals the right of first publication under the terms of the Creative Commons Attribution 4.0 International License.

This license permits unrestricted use, distribution, and reproduction in any medium, including commercial use, provided the original author(s) and source are properly credited. Authors may post and share their published work freely, provided that the original publication in this journal is acknowledged.

By submitting to this journal, authors confirm that their manuscripts are original, not under consideration elsewhere, and that they hold the necessary rights to grant this license. The Functional Food Center encourages open scientific exchange and allows derivative and extended works, provided attribution to the original publication is maintained.