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Danthron Induced Apoptosis Through Mitochondria- and Caspase-3-Dependent Pathways in Human Brain Glioblastoma Multiforms GBM 8401 Cells |
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| Authors: | Hsu-Feng Lu Hai-Lung Wang Ying-Ying Chuang Yih-Jing Tang Jai-Sing Yang Yi-Shih Ma Jo-Hua Chiang Chi-Cheng Lu Jiun-Long Yang Tung-Yuan Lai Chih-Chung Wu Jing-Gung Chung |
| Institution: | 1. Department of Clinical Pathology, Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan 2. College of Human Ecology, Fu-Jen University, Taipei, Taiwan 3. Research Institute of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu, Taiwan 4. Department of Family Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 5. Department of Pharmacology, China Medical University, Taichung, Taiwan 6. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan 7. Department of Chinese Medicine, Chang-Hua Hospital, Changhua, Taiwan 8. Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan 9. School of Chinese Pharmaceutical Science, China Medical University, Taichung, Taiwan 10. Departments of Chinese Internal Medicine, China Medical University Hospital, Taichung, Taiwan 11. School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan 12. Department of Nutrition and Health Science, Chang Jung Christian University, Tainan, Taiwan 13. Department of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, 404, Taichung, Taiwan 14. Department of Biotechnology, Asia University, Wufeng, Taichung, Taiwan |
| Abstract: | Danthron (1,8-dihydroxyanthraquinone), is one of component from Rheum palmatum L. (Polygonaceae), has been shown several biological activities but did not show to induce apoptosis in human brain tumor cells. The aim of this study is to investigate the mechanisms by danthron for the induction of apoptotic potential on human brain glioblastoma multiforms GBM 8401 cell line. Danthron showed a marked concentration- and time-dependent inhibition of GBM 8401 cell viability and induced apoptosis in a dose-and time-dependent manner. There was an attenuation of mitochondrial membrane potential (ΔΨ m ) with the alterations of Bcl-2/Bax protein ratio in GBM 8401 cells, indicating the participation of a mitochondria-related mechanism. Pretreatment of a caspase-8 inhibitor (Z-IETD-FMK), caspase-9 inhibitor (Z-LEHD-FMK) and caspase-3 inhibitor (Z-DEVE-FMK) significantly increased the viable of GBM 8401 cells implied that the participations of caspases. Western blotting analysis also showed the activation of initiator caspase-8 and caspase-9, and executor caspase-3 in GBM 8401 cells. Meanwhile, danthron also promoted the generation of reactive oxygen species (ROS) and cytosolic Ca2+ in GBM 8401 cells. Taken together, our data showed that danthron induced apoptosis in GBM 8401 cells through mitochondria-related and caspase-related pathways, and it may be further evaluated as a chemotherapeutic agent for human brain cancer. |
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