Geranylgeranylacetone induces antiviral gene expression in human hepatoma cells.
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.
Ichikawa
T
T
The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Nakao
K
K
Nakata
K
K
Hamasaki
K
K
Takeda
Y
Y
Kajiya
Y
Y
Higashi
S
S
Ohkubo
K
K
Kato
Y
Y
Ishii
N
N
Eguchi
K
K
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D000998:Antiviral Agents / Q000378:metabolism*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D010766:Phosphorylation; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D019892:eIF-2 Kinase / Q000235:genetics*
D000998:Antiviral Agents; D017931:DNA Primers; D004268:DNA-Binding Proteins; D004224:Diterpenes; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D018168:Receptors, Retinoic Acid; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D019892:eIF-2 Kinase; D015088:2',5'-Oligoadenylate Synthetase; C031049:geranylgeranylacetone