Abstract
Saikosaponin D is a saponin extract derived from several species of Bupleurum (Umbelliferae), which is used for the treatment of various liver diseases in traditional Chinese medicine. In this study, we report that Saikosaponin D inhibits the cell growth of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that Saikosaponin D inhibited the proliferation of A549 by inducing apoptosis and blocking cell cycle progression in the G1 phase. ELISA assay showed that Saikosaponin D significantly increased the expression of p53 and p21/WAF1 protein, contributing to cell cycle arrest. 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. Taken together, our study suggests that the induction of p53 and activity of the Fas/FasL apoptotic system may participate in the antiproliferative activity of Saikosaponin D in A549 cells.
MeSH terms
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Antineoplastic Agents, Phytogenic / pharmacology*
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Apoptosis / drug effects*
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Cycle / drug effects
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Cell Division / drug effects
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Cell Line, Tumor / drug effects
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / metabolism
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DNA, Neoplasm / analysis
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Dose-Response Relationship, Drug
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Enzyme-Linked Immunosorbent Assay
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Fas Ligand Protein
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Flow Cytometry
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Humans
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Medicine, Chinese Traditional*
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Membrane Glycoproteins / metabolism
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Oleanolic Acid / analogs & derivatives*
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Oleanolic Acid / pharmacology*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2*
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Reagent Kits, Diagnostic
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Saponins / pharmacology*
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Tumor Suppressor Protein p53 / metabolism
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bcl-2-Associated X Protein
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fas Receptor / metabolism
Substances
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Antineoplastic Agents, Phytogenic
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BAX protein, human
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DNA, Neoplasm
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FASLG protein, human
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Fas Ligand Protein
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Membrane Glycoproteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Reagent Kits, Diagnostic
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Saponins
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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fas Receptor
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Oleanolic Acid
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saikosaponin D