Suppressive effects of destruxin B on hepatitis B virus surface antigen gene expression in human hepatoma cells.
Destruxin B, a cyclodepsipeptide was originally identified as a plant pathogen from the fungus, Alternaria brassicae. We examined the antiviral activity of destruxin B and found that it suppresses the expression of the hepatitis B viral surface antigen (HBsAg) gene in human hepatoma Hep3B cells which carry an integrated viral gene in its chromosome. In contrast, destruxin B shows no cytotoxic effect on the viability of the cells. Furthermore, it can be shown that destruxin B can reversibly suppress HBsAg production by Hep3B cells in a concentration-dependent manner with EC50 of 0.5 microM. Northern blot analysis indicates that the suppression of HBsAg gene expression by destruxin B is mainly at the mRNA level. Destruxin B not only suppresses the endogenously expressed HBsAg in the Hep3B cells but also suppresses the HBsAg produced either from the stable transfected HBV DNA in another human hepatoma HuH-7 cell line which carry no endogenous HBV genome. These results suggest that destruxin B may have future potential for development as a specific anti-HBV drug.
Chen
H C
HC
Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan, ROC.
Chou
C K
CK
Sun
C M
CM
Yeh
S F
SF
D000998:Antiviral Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D047630:Depsipeptides; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D005814:Genes, Viral / Q000187:drug effects; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis / Q000235:genetics*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D047630:Depsipeptides; D006514:Hepatitis B Surface Antigens; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D012367:RNA, Viral; C040424:destruxin B