Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 7, 2011; 17(13): 1694-1700
Published online Apr 7, 2011. doi: 10.3748/wjg.v17.i13.1694
Legalon-SIL downregulates HCV core and NS5A in human hepatocytes expressing full-length HCV
Marjan Mehrab-Mohseni, Hossein Sendi, Nury Steuerwald, Sriparna Ghosh, Laura W Schrum, Herbert L Bonkovsky
Marjan Mehrab-Mohseni, Hossein Sendi, Nury Steuerwald, Sriparna Ghosh, Laura W Schrum, Herbert L Bonkovsky, The Liver-Biliary-Pancreatic Center, Cannon Research Center, Carolinas Medical Center, Charlotte, NC 28203, United States
Hossein Sendi, Nury Steuerwald, Laura W Schrum, Herbert L Bonkovsky, Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223, United States
Herbert L Bonkovsky, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
Author contributions: Mehrab-Mohseni M performed the research and drafted the paper; Sendi H assisted in the research and revision of the paper; Steuerwald N provided advice regarding the performance of the research; Ghosh S assisted in the the research; Schrum LW provided advice on the the research and revised and contributed to the writing of the paper; Bonkovsky HL designed the research and revised and contributed to the writing of the paper.
Supported by NIH grants R01-DK38825 and contracts N01-DK92326, and U01-DK065201 (Bonkovsky HL)
Correspondence to: Herbert L Bonkovsky, MD, Vice President for Research, The Liver-Biliary-Pancreatic Center, Cannon Research Center, 1000 Blythe Blvd., Charlotte, NC 28203, United States. herbert.bonkovsky@carolinas.org
Telephone: +1-704-3553959 Fax: +1-704-3557648
Received: October 22, 2010
Revised: December 22, 2010
Accepted: December 29, 2010
Published online: April 7, 2011
Abstract

AIM: To determine the effect of Legalon-SIL (LS) on hepatitis C virus (HCV) core and NS5A expression and on heme oxygenase-1 (HMOX-1) and its transcriptional regulators in human hepatoma cells expressing full length HCV genotype 1b.

METHODS: CON1 cells were treated with 50 μmol/L or 200 μmol/L LS. Cells were harvested after 2, 6 and 24 h. HCV RNA and protein levels were determined by quantitative real-time polymerase chain reaction and Western blotting, respectively.

RESULTS: HCV RNA (core and NS5A regions) was decreased after 6 h with LS 200 μmol/L (P < 0.05). Both 50 and 200 μmol/L LS decreased HCV RNA levels [core region (by 55% and 88%, respectively) and NS5A region (by 62% and 87%, respectively) after 24 h compared with vehicle (dimethyl sulphoxide) control (P < 0.01). Similarly HCV core and NS5A protein were decreased (by 85%, P < 0.01 and by 65%, P < 0.05, respectively) by LS 200 μmol/L. Bach1 and HMOX-1 RNA were also downregulated by LS treatment (P < 0.01), while Nrf2 protein was increased (P < 0.05).

CONCLUSION: Our results demonstrate that treatment with LS downregulates HCV core and NS5A expression in CON1 cells which express full length HCV genotype 1b, and suggests that LS may prove to be a valuable alternative or adjunctive therapy for the treatment of HCV infection.

Keywords: Hepatitis; Hepatitis C virus; Silymarin; Silybin; Genotype; Huh7.5; CON1