Abstract
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.
Copyright 2001 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Phytogenic / pharmacology*
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Carcinoma, Hepatocellular
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Carrier Proteins / genetics*
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Cell Cycle Proteins*
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Cell Division / drug effects
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Cell Division / genetics*
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Cyclin-Dependent Kinase Inhibitor p15
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Cyclin-Dependent Kinase Inhibitor p16 / genetics*
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Enzyme Inhibitors / metabolism
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Gene Expression Regulation, Neoplastic / physiology*
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Genes, Tumor Suppressor*
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Humans
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Liver Neoplasms
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Oleanolic Acid* / analogs & derivatives*
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Protein Kinase C / metabolism
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RNA, Messenger / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Sapogenins / pharmacology*
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Saponins*
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Signal Transduction / drug effects
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Tetradecanoylphorbol Acetate / pharmacology*
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Transcription, Genetic* / drug effects
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Tumor Cells, Cultured
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Tumor Suppressor Proteins*
Substances
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Antineoplastic Agents, Phytogenic
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CDKN2B protein, human
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Carrier Proteins
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p15
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Cyclin-Dependent Kinase Inhibitor p16
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Enzyme Inhibitors
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RNA, Messenger
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Sapogenins
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Saponins
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Tumor Suppressor Proteins
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Oleanolic Acid
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Protein Kinase C
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Tetradecanoylphorbol Acetate
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saikosaponin D