Geranylgeranylacetone Induces Antiviral Gene Expression in Human Hepatoma Cells

• Published in: Biochemical and biophysical research communications 2001-01, Vol.280 (3), p.933-939
• Main Authors: Ichikawa, Tatsuki, Nakao, Kazuhiko, Nakata, Keisuke, Hamasaki, Keisuke, Takeda, Yoshio, Kajiya, Yuji, Higashi, Shinichiro, Ohkubo, Kazuaki, Kato, Yuji, Ishii, Nobuko, Eguchi, Katsumi
• Format: Article
• Language: English
• Subjects: 2',5'-Oligoadenylate Synthetase - genetics; 2′5′-oligoadenylate synthetase; Antiviral Agents - metabolism; Base Sequence; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Diterpenes - pharmacology; DNA Primers - genetics; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - metabolism; double-stranded RNA-dependent protein kinase; eIF-2 Kinase - genetics; Gene Expression - drug effects; geranylgeranylacetone; hepatoma cells; Humans; Interferon-Stimulated Gene Factor 3; Interferon-Stimulated Gene Factor 3, gamma Subunit; isoprenoid; Phosphorylation; Receptors, Retinoic Acid - metabolism; signal transducers and activators of transcription 1; STAT1 Transcription Factor; STAT2 Transcription Factor; Trans-Activators - metabolism; Transcription Factors - biosynthesis; Tumor Cells, Cultured
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.4228

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.