Novobiocin modulates cytokeratin assembly and differentiation of human hepatoma cells induced by butyrate and teleocidin.
A differentiation inducer butyrate and a tumor promoter teleocidin had inhibitory effects on the proliferation of PLC/PRF/5 hepatoma. Both of these reagents stimulated the production of procollagen type III peptide, enhanced the cytokeratin assembly and altered the morphological appearance. Novobiocin, a topoisomerase II inhibitor, enhanced the cytokeratin assembly induced by butyrate but antagonized that induced by teleocidin without changing the expression and the phosphorylation state of cytokeratin proteins. In addition, novobiocin acted synergistically with butyrate but not with teleocidin in stimulating the procollagen production and the acetate uptake. These results suggest that butyrate and teleocidin induce cell differentiation via distinct signaling pathway and that novobiocin and butyrate can be used as subsidiary drugs in preventing the growth of hepatoma.
Tsukamoto
A
A
First Department of Medicine, University of Tokyo, Faculty of Medicine, Japan.
Kaneko
Y
Y
Kurokawa
K
K
D000107:Acetylation / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002273:Carcinogens / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007633:Keratins / Q000096:biosynthesis / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced / Q000503:physiopathology; D008235:Lyngbya Toxins / Q000494:pharmacology*; D009675:Novobiocin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000187:drug effects; D011347:Procollagen / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002087:Butyrates; D002273:Carcinogens; D003598:Cytoskeletal Proteins; D008235:Lyngbya Toxins; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D020148:Butyric Acid; D009675:Novobiocin; C022176:teleocidins; D007633:Keratins