Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells
Glioblastoma (GBM) is the most advanced and aggressive form of gliomas. Dihydroartemisinin (DHA) has been shown to exhibit anti-tumor activity in various cancer cells. However, the effect and molecular mechanisms underlying its anti-tumor activity in human GBM cells remain to be elucidated. Our resu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2017.00310/full |
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doaj-8c240565b8174bf1b51ae9cde25b7328 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Chengbin Qu Chengbin Qu Chengbin Qu Jun Ma Jun Ma Jun Ma Xiaobai Liu Xiaobai Liu Xiaobai Liu Yixue Xue Yixue Xue Yixue Xue Jian Zheng Jian Zheng Jian Zheng Libo Liu Libo Liu Libo Liu Jing Liu Jing Liu Jing Liu Zhen Li Zhen Li Zhen Li Lei Zhang Lei Zhang Lei Zhang Yunhui Liu Yunhui Liu Yunhui Liu |
| spellingShingle |
Chengbin Qu Chengbin Qu Chengbin Qu Jun Ma Jun Ma Jun Ma Xiaobai Liu Xiaobai Liu Xiaobai Liu Yixue Xue Yixue Xue Yixue Xue Jian Zheng Jian Zheng Jian Zheng Libo Liu Libo Liu Libo Liu Jing Liu Jing Liu Jing Liu Zhen Li Zhen Li Zhen Li Lei Zhang Lei Zhang Lei Zhang Yunhui Liu Yunhui Liu Yunhui Liu Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells Frontiers in Cellular Neuroscience dihydroartemisinin reactive oxygen species mitochondrion endoplasmic reticulum apoptosis autophagy |
| author_facet |
Chengbin Qu Chengbin Qu Chengbin Qu Jun Ma Jun Ma Jun Ma Xiaobai Liu Xiaobai Liu Xiaobai Liu Yixue Xue Yixue Xue Yixue Xue Jian Zheng Jian Zheng Jian Zheng Libo Liu Libo Liu Libo Liu Jing Liu Jing Liu Jing Liu Zhen Li Zhen Li Zhen Li Lei Zhang Lei Zhang Lei Zhang Yunhui Liu Yunhui Liu Yunhui Liu |
| author_sort |
Chengbin Qu |
| title |
Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells |
| title_short |
Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells |
| title_full |
Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells |
| title_fullStr |
Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells |
| title_full_unstemmed |
Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells |
| title_sort |
dihydroartemisinin exerts anti-tumor activity by inducing mitochondrion and endoplasmic reticulum apoptosis and autophagic cell death in human glioblastoma cells |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Cellular Neuroscience |
| issn |
1662-5102 |
| publishDate |
2017-09-01 |
| description |
Glioblastoma (GBM) is the most advanced and aggressive form of gliomas. Dihydroartemisinin (DHA) has been shown to exhibit anti-tumor activity in various cancer cells. However, the effect and molecular mechanisms underlying its anti-tumor activity in human GBM cells remain to be elucidated. Our results proved that DHA treatment significantly reduced cell viability in a dose- and time-dependent manner by CCK-8 assay. Further investigation identified that the cell viability was rescued by pretreatment either with Z-VAD-FMK, 3-methyladenine (3-MA) or in combination. Moreover, DHA induced apoptosis of GBM cells through mitochondrial membrane depolarization, release of cytochrome c and activation of caspases-9. Enhanced expression of GRP78, CHOP and eIF2α and activation of caspase 12 were additionally confirmed that endoplasmic reticulum (ER) stress pathway of apoptosis was involved in the cytotoxicity of DHA. DHA-treated GBM cells exhibited the morphological and biochemical changes typical of autophagy. Co-treatment with chloroquine (CQ) significantly induced the above effects. Furthermore, ER stress and mitochondrial dysfunction were involved in the DHA-induced autophagy. Further study revealed that accumulation of reactive oxygen species (ROS) was attributed to the DHA induction of apoptosis and autophagy. The illustration of these molecular mechanisms will present a novel insight for the treatment of human GBM. |
| topic |
dihydroartemisinin reactive oxygen species mitochondrion endoplasmic reticulum apoptosis autophagy |
| url |
http://journal.frontiersin.org/article/10.3389/fncel.2017.00310/full |
| work_keys_str_mv |
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doaj-8c240565b8174bf1b51ae9cde25b73282020-11-25T01:08:51ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-09-011110.3389/fncel.2017.00310227611Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma CellsChengbin Qu0Chengbin Qu1Chengbin Qu2Jun Ma3Jun Ma4Jun Ma5Xiaobai Liu6Xiaobai Liu7Xiaobai Liu8Yixue Xue9Yixue Xue10Yixue Xue11Jian Zheng12Jian Zheng13Jian Zheng14Libo Liu15Libo Liu16Libo Liu17Jing Liu18Jing Liu19Jing Liu20Zhen Li21Zhen Li22Zhen Li23Lei Zhang24Lei Zhang25Lei Zhang26Yunhui Liu27Yunhui Liu28Yunhui Liu29Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, ChinaLiaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, ChinaLiaoning Key Laboratory of Neuro-Oncology, Shenyang, ChinaDepartment of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, ChinaKey Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang, ChinaDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, ChinaLiaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, ChinaLiaoning Key Laboratory of Neuro-Oncology, Shenyang, ChinaDepartment of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, ChinaKey Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang, ChinaDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, ChinaLiaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, ChinaLiaoning Key Laboratory of Neuro-Oncology, Shenyang, ChinaDepartment of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, ChinaKey Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang, ChinaDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, ChinaLiaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, ChinaLiaoning Key Laboratory of Neuro-Oncology, Shenyang, ChinaDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, ChinaLiaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, ChinaLiaoning Key Laboratory of Neuro-Oncology, Shenyang, ChinaDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, ChinaLiaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, ChinaLiaoning Key Laboratory of Neuro-Oncology, Shenyang, ChinaDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, ChinaLiaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, ChinaLiaoning Key Laboratory of Neuro-Oncology, Shenyang, ChinaGlioblastoma (GBM) is the most advanced and aggressive form of gliomas. Dihydroartemisinin (DHA) has been shown to exhibit anti-tumor activity in various cancer cells. However, the effect and molecular mechanisms underlying its anti-tumor activity in human GBM cells remain to be elucidated. Our results proved that DHA treatment significantly reduced cell viability in a dose- and time-dependent manner by CCK-8 assay. Further investigation identified that the cell viability was rescued by pretreatment either with Z-VAD-FMK, 3-methyladenine (3-MA) or in combination. Moreover, DHA induced apoptosis of GBM cells through mitochondrial membrane depolarization, release of cytochrome c and activation of caspases-9. Enhanced expression of GRP78, CHOP and eIF2α and activation of caspase 12 were additionally confirmed that endoplasmic reticulum (ER) stress pathway of apoptosis was involved in the cytotoxicity of DHA. DHA-treated GBM cells exhibited the morphological and biochemical changes typical of autophagy. Co-treatment with chloroquine (CQ) significantly induced the above effects. Furthermore, ER stress and mitochondrial dysfunction were involved in the DHA-induced autophagy. Further study revealed that accumulation of reactive oxygen species (ROS) was attributed to the DHA induction of apoptosis and autophagy. The illustration of these molecular mechanisms will present a novel insight for the treatment of human GBM.http://journal.frontiersin.org/article/10.3389/fncel.2017.00310/fulldihydroartemisininreactive oxygen speciesmitochondrionendoplasmic reticulumapoptosisautophagy |