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-tu mor and anti-viral activities in a variety of cell types, we investigated w hether GGA could induce anti-viral proteins in human hepatoma cells. The Hu H-7 and HepG2 cells were treated with GGA, and expression of antiviral prot eins such as 2'5'-oligoadenylate synthetase (2'5'-OAS) and double-stranded RNA-dependent protein kinase (PKR) in these cells was analyzed. GGA stimula ted 2'5'-OAS and PKR gene expression at the transcriptional level through t he formation of interferon-stimulated gene factor 3 (ISGF3), which regulate s both gene transcription. By Western blotting, GGA induced expression of s ignal transducers and activators of transcription 1, 2 (STAT1, STAT2) and p 48 proteins, components of ISGF3, together with the phosphorylation of STAT 1. These results suggest that GC;A acts as a potent inducer of anti-viral g ene expression by stimulating the ISGF3 formation in human hepatoma cells. (C) 2001 Academic Press.