Devaraj Ezhilarasan1, Jonathan Evraerts1, Sid Brice2, Pedro Buc-Calderon3, Sivanesan Karthikeyan4, Etienne Sokal1, Mustapha Najimi1. 1. Institut de Recherche Expérimentale et Clinique (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Université Catholique de Louvain, 1200 Brussels, Belgium. 2. Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, PMNT Unit, Université Catholique de Louvain, 1200 Brussels, Belgium. 3. Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, Chile. 4. Department of Pharmacology and Environmental Toxicology, Food and Hepatotoxicology Laboratory, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Abstract
BACKGROUND: Proliferation of hepatic stellate cells (HSCs) play pivotal role in the progression of hepatic fibrosis consequent to chronic liver injury. Silibinin (SBN), a flavonoid compound, has shown to possess cell cycle arresting potential against many actively proliferating cancers cell lines. The objective of this study was to evaluate the anti-proliferative and cell cycle arresting properties of SBN in rapidly proliferating human hepatic stellate LX-2 cell line. METHODS: LX-2 cells were fed with culture medium supplemented with different concentrations of SBN (10, 50 and 100 μM). After 24 and 96 h of treatment, total cell number was determined by counting. Cytotoxicity was evaluated by trypan blue dye exclusion test. The expression profile of cMyc and peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expressions was evaluated by Western blotting. Oxidative stress marker genes profile was quantified using qPCR. The migratory response of HSCs was observed by scrape wound healing assay. RESULTS: SBN treatments significantly inhibit the LX-2 cell proliferation (without affecting its viability) in dose dependent manner. This treatment also retards the migration of LX-2 cells toward injured area. In Western blotting studies SBN treatment up regulated the protein expressions of PPAR-γ and inhibited cMyc. CONCLUSION: The present study shows that SBN retards the proliferation, activation and migration of LX-2 cells without inducing cytotoxicity and oxidative stress. The profound effects could be due to cell cycle arresting potential of SBN.
BACKGROUND: Proliferation of hepatic stellate cells (HSCs) play pivotal role in the progression of hepatic fibrosis consequent to chronic liver injury. Silibinin (SBN), a flavonoid compound, has shown to possess cell cycle arresting potential against many actively proliferating cancers cell lines. The objective of this study was to evaluate the anti-proliferative and cell cycle arresting properties of SBN in rapidly proliferating human hepatic stellate LX-2 cell line. METHODS: LX-2 cells were fed with culture medium supplemented with different concentrations of SBN (10, 50 and 100 μM). After 24 and 96 h of treatment, total cell number was determined by counting. Cytotoxicity was evaluated by trypan blue dye exclusion test. The expression profile of cMyc and peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expressions was evaluated by Western blotting. Oxidative stress marker genes profile was quantified using qPCR. The migratory response of HSCs was observed by scrape wound healing assay. RESULTS:SBN treatments significantly inhibit the LX-2 cell proliferation (without affecting its viability) in dose dependent manner. This treatment also retards the migration of LX-2 cells toward injured area. In Western blotting studies SBN treatment up regulated the protein expressions of PPAR-γ and inhibited cMyc. CONCLUSION: The present study shows that SBN retards the proliferation, activation and migration of LX-2 cells without inducing cytotoxicity and oxidative stress. The profound effects could be due to cell cycle arresting potential of SBN.
Authors: Zhiming Wen; Todd E Dumas; Sarah J Schrieber; Roy L Hawke; Michael W Fried; Philip C Smith Journal: Drug Metab Dispos Date: 2007-10-03 Impact factor: 3.922
Authors: Eduardo L Guimarães; Leslie Stradiot; Inge Mannaerts; Ben Schroyen; Leo A van Grunsven Journal: Liver Int Date: 2014-10-10 Impact factor: 5.828