Ginsenoside-Rs4, a new type of ginseng saponin concurrently induces apoptosis and selectively elevates protein levels of p53 and p21WAF1 in human hepatoma SK-HEP-1 cells

Eur J Cancer. 1999 Mar;35(3):507-11. doi: 10.1016/s0959-8049(98)00415-8.


In this paper, we present evidence that ginsenoside-Rs4 (G-Rs4; an acetylated analogue of ginsenoside-Rg5), a new ginseng saponin isolated from Panax ginseng C. A. Meyer, elevates protein levels of p53 and p21WAF1, which are associated with the induction of apoptosis in SK-HEP-1 cells. Flow cytometric analyses showed that G-Rs4 initially arrested the cell cycle at the G1/S boundary, but consequently induced apoptosis as evidenced by generating an apoptotic peak. The induction of apoptosis was confirmed by the results of DNA fragmentation assays and alterations in cell morphology after treatment of the cells with G-Rs4. Immunoblot assays showed that G-Rs4 significantly elevated protein levels of p53 and p21WAF1, concurrently with the downregulation of both cyclins E- and A-dependent kinase activities and induction of apoptosis. We suggest that G-Rs4 induces apoptosis, the effect of which is closely related to the downregulation of both cyclins E- and A-dependent kinase activity as a consequence of selectively elevating protein levels of p53 and p21WAF1 in SK-HEP-1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • CDC2-CDC28 Kinases*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / metabolism*
  • Ginsenosides
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Neoplasm Proteins / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Saponins / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism*


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Ginsenosides
  • Neoplasm Proteins
  • Saponins
  • Tumor Suppressor Protein p53
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases