Involvement of p53, nuclear factor kappaB and Fas/Fas ligand in induction of apoptosis and cell cycle arrest by saikosaponin d in human hepatoma cell lines

Cancer Lett. 2004 Sep 30;213(2):213-21. doi: 10.1016/j.canlet.2004.03.044.


In this study, we report the proapoptotic effect of saikosaponin d in two liver cancer cell lines, Hep G2 and Hep 3B cells. Treatment with saikosaponin d decreased the cell proliferation of Hep G2 and Hep 3B cells in a dose dependent manner. In Hep G2, saikosaponin d blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21/WAF1 expression. In addition, an enhancement in Fas/APO-1 and its two form ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), as well as Bax protein, was responsible for the apoptotic effect induced by saikosaponin d. Furthermore, saikosaponin d also inhibited the cell survival signaling by enhancing the amount of IkappaBalpha in cytoplasm and reducing the level and activity of NF-kappaB in the nucleus, and subsequently attenuated the expression of Bcl-XL in Hep G2 and Hep 3B cells. Saikosaponin d therefore decreased the cell proliferation and inducted apoptosis both in p53-positive Hep G2 and p53-negative Hep 3B cells.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle / drug effects*
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Fas Ligand Protein
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / pathology*
  • Membrane Glycoproteins / pharmacology*
  • NF-kappa B / pharmacology*
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology*
  • Proteins / pharmacology*
  • Receptors, Tumor Necrosis Factor*
  • Saponins / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / pharmacology*
  • fas Receptor


  • Antineoplastic Agents, Phytogenic
  • FAS protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • NF-kappa B
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • Saponins
  • Tumor Suppressor Protein p53
  • fas Receptor
  • Oleanolic Acid
  • saikosaponin D