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.
Sun
Hua
H
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan Street, 100050 Beijing, China.
Liu
Geng-Tao
GT
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