Involvement of p-15(INK4b) and p-16(INK4a) gene expression in saikosaponin a and TPA-induced growth inhibition of HepG2 cells

Biochem Biophys Res Commun. 2001 Jul 13;285(2):183-7. doi: 10.1006/bbrc.2001.5152.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carcinoma, Hepatocellular
  • Carrier Proteins / genetics*
  • Cell Cycle Proteins*
  • Cell Division / drug effects
  • Cell Division / genetics*
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Enzyme Inhibitors / metabolism
  • Gene Expression Regulation, Neoplastic / physiology*
  • Genes, Tumor Suppressor*
  • Humans
  • Liver Neoplasms
  • Oleanolic Acid* / analogs & derivatives*
  • Protein Kinase C / metabolism
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sapogenins / pharmacology*
  • Saponins*
  • Signal Transduction / drug effects
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Transcription, Genetic* / drug effects
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*

Substances

  • Antineoplastic Agents, Phytogenic
  • CDKN2B protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • Enzyme Inhibitors
  • RNA, Messenger
  • Sapogenins
  • Saponins
  • Tumor Suppressor Proteins
  • Oleanolic Acid
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • saikosaponin D