Open Access

Tumor-targeting novel manganese complex induces ROS-mediated apoptotic and autophagic cancer cell death

  • Authors:
    • Jia Liu
    • Wenjie Guo
    • Jing Li
    • Xiang Li
    • Ji Geng
    • Qiuyun Chen
    • Jing Gao
  • View Affiliations

  • Published online on: January 20, 2015     https://doi.org/10.3892/ijmm.2015.2073
  • Pages: 607-616
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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


Abstract

In this study, the antitumor activity of the novel manganese (II) compound, Adpa-Mn {[(Adpa)Mn(Cl)(H2O)] (Adpa=bis(2-pyridylmethyl)amino-2-propionic acid)}, and its possible mechanisms of action were investigated. In vitro, the growth inhibitory effects of Adpa-Mn (with IC50 values lower than 15 µM) on tumor cell lines were examined by MTT assay. We found that this compound was more selective against cancer cells than the popular chemotherapeutic reagent, cisplatin. We then found that Adpa-Mn achieved its selectivity against cancer cells through the transferrin (Tf)-transferrin receptor (TfR) system, which is highly expressed in tumor cells. Furthermore, Adpa-Mn induced both apoptosis and autophagy, as indicated by chromatin condensation, the activation of poly(ADP-ribose) polymerase (PARP), Annexin V/propidium iodide staining, an enhanced fluorescence intensity of monodansylcadaverine (MDC), as well as the elevated expression of the autophagy-related protein, microtubule-associated protein 1 light chain 3 (LC3). In addition, Adpa-Mn induced the generation of intracellular reactive oxygen species (ROS) and its anticancer effects were significantly reduced following pre-treatment with the antioxidant, N-acetyl cysteine, indicating that ROS triggered cell death. In vivo, the induction of apoptosis and autophagy in tumor tissue was confirmed following treatment with Adpa-Mn, which contributed to its significant antitumor activity against hepatocellular carcinoma (Hep-A cell) xenografts at 10 mg/kg. Taken together, these data suggest the possible use of Adpa-Mn as a novel anticancer drug.
View Figures
View References

Related Articles

Journal Cover

March-2015
Volume 35 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Liu J, Guo W, Li J, Li X, Geng J, Chen Q and Gao J: Tumor-targeting novel manganese complex induces ROS-mediated apoptotic and autophagic cancer cell death. Int J Mol Med 35: 607-616, 2015.
APA
Liu, J., Guo, W., Li, J., Li, X., Geng, J., Chen, Q., & Gao, J. (2015). Tumor-targeting novel manganese complex induces ROS-mediated apoptotic and autophagic cancer cell death. International Journal of Molecular Medicine, 35, 607-616. https://doi.org/10.3892/ijmm.2015.2073
MLA
Liu, J., Guo, W., Li, J., Li, X., Geng, J., Chen, Q., Gao, J."Tumor-targeting novel manganese complex induces ROS-mediated apoptotic and autophagic cancer cell death". International Journal of Molecular Medicine 35.3 (2015): 607-616.
Chicago
Liu, J., Guo, W., Li, J., Li, X., Geng, J., Chen, Q., Gao, J."Tumor-targeting novel manganese complex induces ROS-mediated apoptotic and autophagic cancer cell death". International Journal of Molecular Medicine 35, no. 3 (2015): 607-616. https://doi.org/10.3892/ijmm.2015.2073