title: Saikosaponin a Induces Apoptosis through Mitochondria-Dependent Pathway in Hepatic Stellate Cells.
abstract: Saikosaponin a (SSa) is one of the main active components of Bupleurum falcatum. It is commonly used to treat liver injury and fibrosis in traditional Chinese medicine. Our previous study showed that SSa induces apoptosis and inhibits the proliferation of rat hepatic stellate cell (HSC) line HSC-T6. The aim of the present study was to elucidate the mechanism of SSa-mediated apoptosis. Rat HSC cell line HSC-T6 and human HSC cell line LX-2 were used in this study. SSa triggered cell death mainly by apoptosis, as indicated by the typical morphological changes, sub-G1 phase of cell cycle increase, and activation of the caspase-9/caspase-3 cascade. In addition, SSa-induced apoptosis was partially inhibited by the caspase-3 inhibitor Z-DEVD-FMK, suggesting an involvement of caspase-3 dependent and independent pathways. Moreover, SSa upregulated pro-apoptotic proteins [BAK, Bcl-2-associated death promoter (BAD), and p53 upregulated modulator of apoptosis (PUMA)] and downregulated anti-apoptotic proteins (Bcl-2). In the mitochondria, SSa triggered the translocation of BAX and BAK from the cytosol to the outer membrane, resulting in a reduction of mitochondrial functions and membrane potential and subsequent release of apoptotic factors. Therefore, this study demonstrates that SSa induces apoptosis through the intrinsic mitochondrial-dependent pathway in HSCs.
authors.affiliation: * Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|† Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.|‡ Department of Applied Chemistry and Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Taiwan.
authors.forename: Chang-Han
authors.initials: CH
authors.lastname: Chen
authors.affiliation: § Department of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan.|¶ Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Chen
authors.affiliation: ∥ Department of Obstetrics and Gynecology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.|¶¶ Department of Obstetrics and Gynecology, University of South Florida, College of Medicine, Tampa, Florida.
authors.forename: S Joseph
authors.initials: SJ
authors.lastname: Huang
authors.affiliation: ∥ Department of Obstetrics and Gynecology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Huang
authors.affiliation: ** Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Hao-Kuang
authors.initials: HK
authors.lastname: Wang
authors.affiliation: †† Department of Biological Science & Technology, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Wen-Chuan
authors.initials: WC
authors.lastname: Hsieh
authors.affiliation: ∥∥ Institute of Biotechnology, National Changhua University of Education, Changhua, Taiwan.|*** Laboratory of Animal Center, Department of Medical Research and Development, Show Chwan Health Care System, Changhua, Taiwan.
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Huang
authors.affiliation: ‡‡ School of Medicine, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Liu
authors.affiliation: §§ Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.|††† Cell Therapy and Research Center, Department of Medical Research, E-Da Cancer Hospital, Kaohsiung, Taiwan.
authors.forename: Li-Yen
authors.initials: LY
authors.lastname: Shiu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D029972:Bupleurum; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D055166:Hepatic Stellate Cells / Q000166:cytology*; D008928:Mitochondria / Q000378:metabolism*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D012503:Saponins / Q000494:pharmacology*; D013268:Stimulation, Chemical
chemical_list: D012503:Saponins; D009828:Oleanolic Acid; D053148:Caspase 3; C025759:saikosaponin D
keywords: Apoptosis; Bupleurum falcatum; Caspase-3; Hepatic Stellate Cells; Mitochondria; Sakosaponin A