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Article

Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway

  • Authors:
    • Bor-Chin Cheng
    • Jui-Tai Chen
    • Shun-Tai Yang
    • Chung-Ching Chio
    • Shing-Hwa Liu
    • Ruei-Ming Chen
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Chi-Mei Medical Center, Tainan, Taiwan, R.O.C., Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan, R.O.C., Department of Neurosurgery, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, R.O.C., Department of Neurosurgery, Chi-Mei Medical Center, Tainan, Taiwan, R.O.C., Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C., Comprehensive Cancer Center, Taipei Medical University, Taipei, Taiwan, R.O.C.
  • Pages: 964-974
    |
    Published online on: January 25, 2017
       https://doi.org/10.3892/ijo.2017.3861
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Abstract

Malignant glioma is the most aggressive brain tumor. Hypoxic condition has been explored for killing cancer stem cells or drug-resistant tumor cells. This study investigated the effects of hypoxia on autophagic death and the possible mechanisms. Exposure of human malignant glioma U87-MG cells to cobalt chloride (CoCl2) increased cellular hypoxia-inducible factor-1α levels and concurrently decreased cell viability concentration- and time-dependently. In parallel, treatment with CoCl2 suppressed proliferation of human U87-MG cells. Autophagic cells and levels of LC3-II were concentration- and time-dependently induced in human U87-MG cells after exposure to CoCl2. However, pretreatment with 3-mehyladenine (3-MA) and chloroquine, inhibitors of cell autophagy, caused significant alleviations in CoCl2-induced cell autophagy. In contrast, exposure to rapamycin, an inducer of cell autophagy, synergistically induced hypoxia-induced autophagy of U87-MG cells. Administration of human U87-MG cells with CoCl2 triggered caspase-3 activation and cell apoptosis. Interestingly, pretreatment with 3-MA and chloroquine remarkably suppressed CoCl2-induced caspase-3 activation and cell apoptosis. Application of p53 small interference (si)RNA into human U87-MG cells downregulated levels of this protein and simultaneously lowered hypoxia- and 3-MA-induced alterations in cell autophagy, apoptosis, and death. The hypoxia-induced autophagy and apoptosis of DBTRG-05MG cells were significantly lowered by 3-MA pretreatment and p53 knockdown. Therefore, the present study shows that CoCl2 treatment can induce autophagy of human glioma cells and subsequent autophagic apoptosis via a p53-dependent pathway. Hypoxia-induced autophagic apoptosis may be applied as a therapeutic strategy for treatment of glioma patients.
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Copy and paste a formatted citation
Spandidos Publications style
Cheng B, Chen J, Yang S, Chio C, Liu S and Chen R: Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway. Int J Oncol 50: 964-974, 2017.
APA
Cheng, B., Chen, J., Yang, S., Chio, C., Liu, S., & Chen, R. (2017). Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway. International Journal of Oncology, 50, 964-974. https://doi.org/10.3892/ijo.2017.3861
MLA
Cheng, B., Chen, J., Yang, S., Chio, C., Liu, S., Chen, R."Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway". International Journal of Oncology 50.3 (2017): 964-974.
Chicago
Cheng, B., Chen, J., Yang, S., Chio, C., Liu, S., Chen, R."Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway". International Journal of Oncology 50, no. 3 (2017): 964-974. https://doi.org/10.3892/ijo.2017.3861
Copy and paste a formatted citation
x
Spandidos Publications style
Cheng B, Chen J, Yang S, Chio C, Liu S and Chen R: Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway. Int J Oncol 50: 964-974, 2017.
APA
Cheng, B., Chen, J., Yang, S., Chio, C., Liu, S., & Chen, R. (2017). Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway. International Journal of Oncology, 50, 964-974. https://doi.org/10.3892/ijo.2017.3861
MLA
Cheng, B., Chen, J., Yang, S., Chio, C., Liu, S., Chen, R."Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway". International Journal of Oncology 50.3 (2017): 964-974.
Chicago
Cheng, B., Chen, J., Yang, S., Chio, C., Liu, S., Chen, R."Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway". International Journal of Oncology 50, no. 3 (2017): 964-974. https://doi.org/10.3892/ijo.2017.3861
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