title: Legalon-SIL downregulates HCV core and NS5A in human hepatocytes expressing full-length HCV.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Liver-Biliary-Pancreatic Center, Cannon Research Center, Carolinas Medical Center, Charlotte, NC 28203, United States.
authors.forename: Marjan
authors.initials: M
authors.lastname: Mehrab-Mohseni
authors.forename: Hossein
authors.initials: H
authors.lastname: Sendi
authors.forename: Nury
authors.initials: N
authors.lastname: Steuerwald
authors.forename: Sriparna
authors.initials: S
authors.lastname: Ghosh
authors.forename: Laura W
authors.initials: LW
authors.lastname: Schrum
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology / Q000821:virology*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012838:Silymarin / Q000494:pharmacology*; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000975:Antioxidants; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; D051547:Heme Oxygenase-1; D051267:NF-E2-Related Factor 2; D012367:RNA, Viral; D012838:Silymarin; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C102108:BACH1 protein, human; C495635:NFE2L2 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase