Chemopreventive effect of bicyclol on malignant transformation of WB-F344 rat liver epithelial cells and its effect on related signal transduction in vitro.
The preventive effect of bicyclol, a novel anti-hepatitis drug, on hepatocarcinogenesis and its mechanism of action was studied in vitro. The results clearly indicated that bicyclol at non-toxic doses prevented the malignant transformation of WB-F344 cells (WB cells) induced by 3-methylcholanthrene (3MC) and 12-O-tetradecanoyl phorbol 13-acetate (TPA). Furthermore, bicyclol inhibited proliferation of quiescent WB cells stimulated by TPA and blocked TPA-induced down-regulation of the gap junctional intercellular communication (GJIC). Immunoblot analysis demonstrated that bicyclol exhibited a remarkable reversing effect on TPA-induced cPKC-alpha and phosphor-ERK1/2 expressions. In addition, bicyclol attenuated TPA-induced IkappaB-alpha degradation. In conclusion, our results support that bicyclol has chemopreventive action against hepatocarcinogenesis through inhibition of related signal transduction.
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan Street, 100050 Beijing, China.
Hua
H
Sun
Geng-Tao
GT
Liu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001551:Benz(a)Anthracenes; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008748:Methylcholanthrene; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D051571:Protein Kinase C-alpha / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate
D000970:Antineoplastic Agents; D001551:Benz(a)Anthracenes; D001713:Biphenyl Compounds; D020672:I-kappa B Proteins; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha; D008748:Methylcholanthrene; C477843:bicyclol; D051571:Protein Kinase C-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013755:Tetradecanoylphorbol Acetate