geranylgeranylacetone and Carcinoma--Hepatocellular

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.

Topics: 2',5'-Oligoadenylate Synthetase; Antiviral Agents; Base Sequence; Carcinoma, Hepatocellular; Diterpenes; DNA Primers; DNA-Binding Proteins; eIF-2 Kinase; Gene Expression; Humans; Interferon-Stimulated Gene Factor 3; Interferon-Stimulated Gene Factor 3, gamma Subunit; Phosphorylation; Receptors, Retinoic Acid; STAT1 Transcription Factor; STAT2 Transcription Factor; Trans-Activators; Transcription Factors; Tumor Cells, Cultured

Since gastric mucosal lesions are frequently encountered in patients with liver disease, we measured the levels of gastric mucosal hexosamine. In chronic hepatitis patients, hexosamine levels were reduced in both the antrum and corpus as compared with those in normal controls, while values in the advanced liver cirrhosis group (total bilirubin greater than 5 mg/dl) were lower than in the less advanced group. Although the presence or absence of esophageal varices had no influence on hexosamine, higher concentrations were found in patients with the red color sign (+) in comparison with those with negative red color sign (-). One month after endoscopic injection sclerotherapy of esophageal varices, hexosamine did not change, but decreases were seen in both the antrum and corpus at 3 months. We observed an increase in gastric mucosal blood flow after treatment with teprenone, a new antiulcerative agent, in normal controls. Gastric mucosal hexosamine increased significantly after teprenone treatment in both chronic hepatitis and liver cirrhosis groups. From these results, we conclude that hexosamine has a defensive action against gastric lesions in various liver diseases.

Topics: Anti-Ulcer Agents; Carcinoma, Hepatocellular; Diterpenes; Duodenal Ulcer; Female; Gastric Mucosa; Hexosamines; Humans; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Stomach Ulcer