18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways
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 ti...
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MDPI AG
2016-07-01
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| Online Access: | http://www.mdpi.com/1420-3049/21/7/872 |
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| author | Yi-Chang Huang Chao-Lin Kuo Kung-Wen Lu Jen-Jyh Lin Jiun-Long Yang Rick Sai-Chuen Wu Ping-Ping Wu Jing-Gung Chung |
| author_facet | Yi-Chang Huang Chao-Lin Kuo Kung-Wen Lu Jen-Jyh Lin Jiun-Long Yang Rick Sai-Chuen Wu Ping-Ping Wu Jing-Gung Chung |
| author_sort | Yi-Chang Huang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T19:53:16Z |
| format | Article |
| id | doaj.art-ed29212ba57545a9ae1aa187dc7e0e3b |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T19:53:16Z |
| publishDate | 2016-07-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ed29212ba57545a9ae1aa187dc7e0e3b2022-12-22T02:32:26ZengMDPI AGMolecules1420-30492016-07-0121787210.3390/molecules21070872molecules2107087218α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling PathwaysYi-Chang Huang0Chao-Lin Kuo1Kung-Wen Lu2Jen-Jyh Lin3Jiun-Long Yang4Rick Sai-Chuen Wu5Ping-Ping Wu6Jing-Gung Chung7Department of Biological Science and Technology, China Medical University, Taichung 404, TaiwanDepartment of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, TaiwanCollege of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 404, TaiwanDivision of Cardiology, China Medical University Hospital, Taichung 404, TaiwanDepartment of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, TaiwanDepartment of Anesthesiology, China Medical University Hospital, Taichung 404, TaiwanSchool of Pharmacy, China Medical University, Taichung 404, TaiwanDepartment of Biological Science and Technology, China Medical University, Taichung 404, TaiwanIn 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.http://www.mdpi.com/1420-3049/21/7/87218α-glycyrrhetinic acidmitochondriacaspase-3apoptosisHL-60 cells |
| spellingShingle | Yi-Chang Huang Chao-Lin Kuo Kung-Wen Lu Jen-Jyh Lin Jiun-Long Yang Rick Sai-Chuen Wu Ping-Ping Wu Jing-Gung Chung 18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways Molecules 18α-glycyrrhetinic acid mitochondria caspase-3 apoptosis HL-60 cells |
| title | 18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways |
| title_full | 18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways |
| title_fullStr | 18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways |
| title_full_unstemmed | 18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways |
| title_short | 18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways |
| title_sort | 18α glycyrrhetinic acid induces apoptosis of hl 60 human leukemia cells through caspases and mitochondria dependent signaling pathways |
| topic | 18α-glycyrrhetinic acid mitochondria caspase-3 apoptosis HL-60 cells |
| url | http://www.mdpi.com/1420-3049/21/7/872 |
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