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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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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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Acknowledgments

This work was supported by Grant CMU95-075 from China Medical University, Taichung, Taiwan.

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Authors and Affiliations

  1. Department of Clinical Pathology, Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan

    Hsu-Feng Lu

  2. College of Human Ecology, Fu-Jen University, Taipei, Taiwan

    Hsu-Feng Lu

  3. Research Institute of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu, Taiwan

    Hai-Lung Wang & Ying-Ying Chuang

  4. Department of Family Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

    Yih-Jing Tang

  5. Department of Pharmacology, China Medical University, Taichung, Taiwan

    Jai-Sing Yang

  6. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan

    Yi-Shih Ma

  7. Department of Chinese Medicine, Chang-Hua Hospital, Changhua, Taiwan

    Yi-Shih Ma

  8. Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan

    Jo-Hua Chiang & Chi-Cheng Lu

  9. School of Chinese Pharmaceutical Science, China Medical University, Taichung, Taiwan

    Jiun-Long Yang

  10. Departments of Chinese Internal Medicine, China Medical University Hospital, Taichung, Taiwan

    Tung-Yuan Lai

  11. School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan

    Tung-Yuan Lai

  12. Department of Nutrition and Health Science, Chang Jung Christian University, Tainan, Taiwan

    Chih-Chung Wu

  13. Department of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, 404, Taichung, Taiwan

    Jing-Gung Chung

  14. Department of Biotechnology, Asia University, Wufeng, Taichung, Taiwan

    Jing-Gung Chung

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  1. Hsu-Feng Lu
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Correspondence to Jing-Gung Chung.

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Lu, HF., Wang, HL., Chuang, YY. et al. Danthron Induced Apoptosis Through Mitochondria- and Caspase-3-Dependent Pathways in Human Brain Glioblastoma Multiforms GBM 8401 Cells. Neurochem Res 35, 390–398 (2010). https://doi.org/10.1007/s11064-009-0067-9

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  • DOI: https://doi.org/10.1007/s11064-009-0067-9

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