title: Combined taurine, epigallocatechin gallate and genistein therapy reduces HSC-T6 cell proliferation and modulates the expression of fibrogenic factors.
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.
authors.affiliation: Guangxi University Library, Guangxi University, Nanning 530004, Guangxi, China. lminggx@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.forename: Xuerong
authors.initials: X
authors.lastname: Zhang
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.forename: Ming
authors.initials: M
authors.lastname: Liao
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004359:Drug Therapy, Combination / Q000379:methods; D019833:Genistein / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013654:Taurine / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D024042:Collagen Type I; D012333:RNA, Messenger; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D019716:Tissue Inhibitor of Metalloproteinase-2; D013654:Taurine; D002392:Catechin; C045651:epigallocatechin gallate; D019833:Genistein; D020778:Matrix Metalloproteinase 2