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.

Abstract

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.

• Authors: Ya-Ling Hsu, Po-Lin Kuo, Lien-Chai Chiang, Chun-Ching Lin
• Journal: Cancer letters (Cancer Lett) Vol. 213 Issue 2 Pg. 213-21 (Sep 30 2004) ISSN: 0304-3835 [Print] Ireland
• PMID: 15327837 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• 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, pharmacology)
• Proteins (pharmacology)
• Receptors, Tumor Necrosis Factor
• Saponins (pharmacology)
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (pharmacology)
• fas Receptor