Open Access

A novel manganese complex selectively induces malignant glioma cell death by targeting mitochondria

  • Authors:
    • Ji Geng
    • Jing Li
    • Tao Huang
    • Kaidi Zhao
    • Qiuyun Chen
    • Wenjie Guo
    • Jing Gao
  • View Affiliations

  • Published online on: July 12, 2016     https://doi.org/10.3892/mmr.2016.5509
  • Pages: 1970-1978
  • Copyright: © Geng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Despite advances in treatment, malignant glioma commonly exhibits recurrence, subsequently leading to a poor prognosis. As manganese (Mn) compounds can be transported by the transferrin‑transferrin receptor system, the present study synthesized and examined the potential use of Adpa‑Mn as a novel antitumor agent. Adpa‑Mn time and dose‑dependently inhibited U251 and C6 cell proliferation; however, it had little effect on normal astrocytes. Apoptosis was significantly elevated following treatment with Adpa‑Mn, as detected by chromatin condensation, Annexin V/propidium iodide staining, cytochrome c release from mitochondria to the cytoplasm, and the activation of caspases‑9, ‑7 and ‑3 and poly (ADP‑ribose) polymerase. In addition, Adpa‑Mn enhanced fluorescence intensity of monodansylcadaverine and elevated the expression levels of the autophagy‑related protein microtubule‑associated protein 1 light chain 3. Pretreatment with the autophagy inhibitors 3‑methyladenine and chloroquine enhanced Adpa‑Mn‑induced cell inhibition, thus indicating that autophagy has an essential role in this process. Furthermore, evidence of mitochondrial dysfunction was detected in the Adpa‑Mn‑treated group, including disrupted membrane potential, elevated levels of reactive oxygen species (ROS) and depleted adenosine triphosphate. Conversely, treatment with the mitochondrial permeability transition inhibitor cyclosporin A reversed Adpa‑Mn‑induced ROS production, mitochondrial damage and cell apoptosis, thus suggesting that Adpa‑Mn may target the mitochondria. Taken together, these data suggested that Adpa‑Mn may be considered for use as a novel anti‑glioma therapeutic option.
View Figures
View References

Related Articles

Journal Cover

September-2016
Volume 14 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Geng J, Li J, Huang T, Zhao K, Chen Q, Guo W and Gao J: A novel manganese complex selectively induces malignant glioma cell death by targeting mitochondria. Mol Med Rep 14: 1970-1978, 2016
APA
Geng, J., Li, J., Huang, T., Zhao, K., Chen, Q., Guo, W., & Gao, J. (2016). A novel manganese complex selectively induces malignant glioma cell death by targeting mitochondria. Molecular Medicine Reports, 14, 1970-1978. https://doi.org/10.3892/mmr.2016.5509
MLA
Geng, J., Li, J., Huang, T., Zhao, K., Chen, Q., Guo, W., Gao, J."A novel manganese complex selectively induces malignant glioma cell death by targeting mitochondria". Molecular Medicine Reports 14.3 (2016): 1970-1978.
Chicago
Geng, J., Li, J., Huang, T., Zhao, K., Chen, Q., Guo, W., Gao, J."A novel manganese complex selectively induces malignant glioma cell death by targeting mitochondria". Molecular Medicine Reports 14, no. 3 (2016): 1970-1978. https://doi.org/10.3892/mmr.2016.5509