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Geranylgeranylacetone induces antiviral gene expression in human hepatoma cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2001 Jan 26; Vol. 280 (3), pp. 933-9. - Publication Year :
- 2001
-
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.<br /> (Copyright 2001 Academic Press.)
- Subjects :
- Base Sequence
Carcinoma, Hepatocellular metabolism
DNA Primers genetics
DNA-Binding Proteins biosynthesis
DNA-Binding Proteins metabolism
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
2',5'-Oligoadenylate Synthetase genetics
Antiviral Agents metabolism
Carcinoma, Hepatocellular drug therapy
Carcinoma, Hepatocellular genetics
Diterpenes pharmacology
eIF-2 Kinase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 280
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 11162614
- Full Text :
- https://doi.org/10.1006/bbrc.2000.4228