Combined taurine, epigallocatechin gallate and genistein therapy reduces HSC-T6 cell proliferation and modulates the expression of fibrogenic factors

Int J Mol Sci. 2013 Oct 14;14(10):20543-54. doi: 10.3390/ijms141020543.

Abstract

Hepatic fibrogenesis involves the activation of hepatic stellate cells (HSCs), which synthesize excess extracellular matrix and contribute to the development of liver fibrosis. In a prior study we tested the effect of combined treatment with taurine, epigallocatechin gallate and genistein on the development of alcohol-induced liver fibrosis in vitro. In this study, the biological activity of the combination of these molecules was assessed by measuring its effect on cell proliferation, fibrosis-related gene expression, and proteomic expression profiling in the activated HSC cell line, HSC-T6. HSC-T6 cells were incubated with different concentrations of the drug combination taurine, epigallocatechin gallate and genistein. Cell proliferation was evaluated by MTT assay. Transforming growth factor β1 (TGF-β1), collagen type I (Col-I), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) mRNA were analyzed by semi-quantitative reverse-transcription PCR. Proteomic profiling of HSC-T6 cells was also performed by SELDI-TOF-MS. Combined drug treatment significantly inhibited cell proliferation and TGF-β1, Col-I, TIMP-1 and TIMP-2 mRNA expression in activated HSC-T6 cells, while the expression of MMP-2 mRNA increased. A total of 176 protein m/z peaks were identified. The intensities of 10 protein peaks were downregulated and two protein peaks were upregulated in HSC-T6 cells after combined drug treatment. In conclusion, combined drug treatment with taurine, epigallocatechin gallate and genistein can inhibit HSC proliferation, and impact fibrosis-related gene and protein expression. The antifibrotic effects of this drug combination may be due to its effects on the expression of fibrogenic genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Line
  • Cell Proliferation / drug effects*
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Drug Therapy, Combination / methods
  • Genistein / pharmacology*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • RNA, Messenger / genetics
  • Rats
  • Taurine / pharmacology*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Up-Regulation / drug effects

Substances

  • Collagen Type I
  • RNA, Messenger
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta1
  • Tissue Inhibitor of Metalloproteinase-2
  • Taurine
  • Catechin
  • epigallocatechin gallate
  • Genistein
  • Matrix Metalloproteinase 2