Document Detail


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.
MedLine Citation:
PMID:  15327837     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer letters     Volume:  213     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-25     Completed Date:  2004-11-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  213-21     Citation Subset:  IM    
Affiliation:
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Road, 807, Taiwan, ROC.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD95
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*
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/Antineoplastic Agents, Phytogenic; 0/FAS protein, human; 0/FASLG protein, human; 0/Fas Ligand Protein; 0/Membrane Glycoproteins; 0/NF-kappa B; 0/Proteins; 0/Receptors, Tumor Necrosis Factor; 0/Saponins; 0/Tumor Suppressor Protein p53; 20874-52-6/saikosaponin; 508-02-1/Oleanolic Acid

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