Involvement of p-15(INK4b) and p-16(INK4a) gene expression in saikosaponin a and TPA-induced growth inhibition of HepG2 cells.
Saikosaponin a, a purified ingredient of Chinese herb with known antitumor activity, can inhibit cell growth and DNA synthesis of hepatoma cell line HepG2. Both mRNA and protein of the CDK inhibitor p-16(INK4a) and p-15(INK4b) in HepG2 were greatly induced by saikosaponin a while that of p-21(CIP), p-27(KIP) and other cell cycle related genes were not. In addition, reduced phosphorylation of RB protein is observed in saikosaponin a-treated HepG2. Staurosporin, one of the PKC inhibitors, significantly prevented the saikosaponin a induced growth inhibition suggesting PKC pathway be involved. On the other hand, the phorbol ester tumor promoter TPA (12-O-Tetredecanolyphorbol 13-acetate) also inhibited HepG2 growth and specifically induced p-16(INK4a) and p-15(INK4b) mRNA expression. The results suggest that both saikosaponin a and TPA-induced HepG2 growth inhibition are associated with p-15(INK4a) and p-16(INK4b) gene expression and might be mediated by PKC signaling pathway.
Wu
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WS
Department of Medical Technology, Tzu Chi University, No. 701, Chung Yang Rd., Sec. 3, Hualien, Taiwan 970. wuws@mail.tcu.edu.tw
Hsu
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D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms; D009828:Oleanolic Acid / Q000031:analogs & derivatives*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012502:Sapogenins / Q000494:pharmacology*; D012503:Saponins; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D000972:Antineoplastic Agents, Phytogenic; C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D012502:Sapogenins; D012503:Saponins; D025521:Tumor Suppressor Proteins; D009828:Oleanolic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C025759:saikosaponin D