Geranylgeranylacetone induces antiviral gene expression in human hepatoma cells

Biochem Biophys Res Commun. 2001 Jan 26;280(3):933-9. doi: 10.1006/bbrc.2000.4228.

Abstract

Geranylgeranylacetone (GGA), an isoprenoid compound, is used clinically as an anti-ulcer drug. Since some isoprenoids including retinoids have anti-tumor and anti-viral activities in a variety of cell types, we investigated whether GGA could induce anti-viral proteins in human hepatoma cells. The HuH-7 and HepG2 cells were treated with GGA, and expression of anti-viral proteins such as 2'5'-oligoadenylate synthetase (2'5'-OAS) and double-stranded RNA-dependent protein kinase (PKR) in these cells was analyzed. GGA stimulated 2'5'-OAS and PKR gene expression at the transcriptional level through the formation of interferon-stimulated gene factor 3 (ISGF3), which regulates both gene transcription. By Western blotting, GGA induced expression of signal transducers and activators of transcription 1, 2 (STAT1, STAT2) and p48 proteins, components of ISGF3, together with the phosphorylation of STAT1. These results suggest that GGA acts as a potent inducer of anti-viral gene expression by stimulating the ISGF3 formation in human hepatoma cells.

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics*
  • Antiviral Agents / metabolism*
  • Base Sequence
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • DNA Primers / genetics
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / metabolism
  • Diterpenes / pharmacology*
  • Gene Expression / drug effects
  • Humans
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Phosphorylation
  • Receptors, Retinoic Acid / metabolism
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • Trans-Activators / metabolism
  • Transcription Factors / biosynthesis
  • Tumor Cells, Cultured
  • eIF-2 Kinase / genetics*

Substances

  • Antiviral Agents
  • DNA Primers
  • DNA-Binding Proteins
  • Diterpenes
  • IRF9 protein, human
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Receptors, Retinoic Acid
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT2 Transcription Factor
  • STAT2 protein, human
  • Trans-Activators
  • Transcription Factors
  • eIF-2 Kinase
  • 2',5'-Oligoadenylate Synthetase
  • geranylgeranylacetone