The proliferative inhibition and apoptotic mechanism of Saikosaponin D in human non-small cell lung cancer A549 cells.
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.
Hsu
Ya-Ling
YL
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Road, Kaohsiung 807, Taiwan.
Kuo
Po-Lin
PL
Lin
Chun-Ching
CC
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008516:Medicine, Chinese Traditional; D008562:Membrane Glycoproteins / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D011933:Reagent Kits, Diagnostic; D012503:Saponins / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011933:Reagent Kits, Diagnostic; D012503:Saponins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D009828:Oleanolic Acid; C025759:saikosaponin D