title: 18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways.
abstract: In this study we investigate the molecular mechanisms of caspases and mitochondria in the extrinsic and intrinsic signal apoptosis pathways in human leukemia HL-60 cells after in vitro exposure to 18α-glycyrrhetinic acid (18α-GA). Cells were exposed to 18α-GA at various concentrations for various time periods and were harvested for flow cytometry total viable cell and apoptotic cell death measurements. Cells treated with 18α-GA significantly inhibited cell proliferation and induced cell apoptosis in a dose-dependent manner, with an IC50 value of 100 μM at 48 h. The cell growth inhibition resulted in induction of apoptosis and decreased the mitochondria membrane potential (ΔΨm) and increased caspase-8, -9 and -3 activities. Furthermore, cytochrome c and AIF were released from mitochondria, as shown by western blotting and confirmed by confocal laser microscopy. Western blotting showed that 18α-GA increased the levels of pro-apoptotic proteins such as Bax and Bid and decreased the anti-apoptotic proteins such as Bcl-2 and Bcl-xl, furthermore, results also showed that 18α-GA increased Fas and Fas-L which are associated with surface death receptor in HL-60 cells. Based on those observations, the present study supports the hypothesis that 18α-GA-induced apoptosis in HL-60 cells involves the activation of the both extrinsic and intrinsic apoptotic pathways.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan. YCH@mail.cmu.edu.tw.
authors.forename: Yi-Chang
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan. clkuo@mail.cmu.edu.tw.
authors.forename: Chao-Lin
authors.initials: CL
authors.lastname: Kuo
authors.affiliation: College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 404, Taiwan. prorna@mail.cmu.edu.tw.
authors.forename: Kung-Wen
authors.initials: KW
authors.lastname: Lu
authors.affiliation: Division of Cardiology, China Medical University Hospital, Taichung 404, Taiwan. pig222@ms15.hinet.net.
authors.forename: Jen-Jyh
authors.initials: JJ
authors.lastname: Lin
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan. JLY@mail.cmu.edu.tw.
authors.forename: Jiun-Long
authors.initials: JL
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, China Medical University Hospital, Taichung 404, Taiwan. rickwu@mail.cmuh.org.tw.|Department of Medicine, China Medical University, Taichung 404, Taiwan. rickwu@mail.cmuh.org.tw.
authors.forename: Rick Sai-Chuen
authors.initials: RS
authors.lastname: Wu
authors.affiliation: School of Pharmacy, China Medical University, Taichung 404, Taiwan. ppwu@mail.cmu.edu.tw.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Wu
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan. jgchung@mail.cmu.edu.tw.|Department of Biotechnology, Asia University, Taichung 413, Taiwan. jgchung@mail.cmu.edu.tw.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D015870:Gene Expression; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C119129:18alpha-glycyrrhetinic acid; D020169:Caspases; D006034:Glycyrrhetinic Acid
keywords: 18α-glycyrrhetinic acid; HL-60 cells; apoptosis; caspase-3; mitochondria