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BioMetals

, Volume 28, Issue 2, pp 267–278 | Cite as

Antiproliferative effects of copper(II)–polypyridyl complexes in breast cancer cells through inducing apoptosis

  • Mona Salimi
  • Khatereh Abdi
  • Hirsa Mostafapour Kandelous
  • Hassan Hadadzadeh
  • Kayhan Azadmanesh
  • Amir Amanzadeh
  • Hassan Sanati
Article

Abstract

Although cisplatin has been used for decades to treat human cancer, some toxic side effects and resistance are observed. Previous investigations have suggested copper complexes as a novel class of tumor-cell apoptosis inducers. The present study aimed to evaluate the anti-breast cancer activities of two polypyridyl-based copper(II) complexes, [Cu(tpy)(dppz)](NO3)2 (1) and [Cu(tptz)2](NO3)2 (2) (tpy = 2,2′:6′,2″-terpyridine, dppz = dipyrido[3,2-a:2′,3′-c]phenazine, tptz = 2,4,6-tris(2-pyridyl)-1,3,5-triazine), using human breast adenocarcinoma cell line (MCF-7). The ability of the complexes to cleave supercoiled DNA in the presence and absence of external agents was also examined. The apoptotic activities of the complexes were assessed using flow cytometry, fluorescence microscope and western blotting analysis. Our results indicated the high DNA affinity and nuclease activity of complexes 1 and 2. The cleavage mechanisms between the complexes and plasmid DNA are likely to involve a singlet oxygen or singlet oxygen-like entity as the reactive oxygen species. Complexes 1 and 2 also significantly inhibited the proliferation of MCF-7 cells in a dose-dependent manner (IC50 values = 4.57 and 1.98 μM at 24 h, respectively). Complex 2 remarkably induced MCF-7 cells to undergo apoptosis, which was demonstrated by cell morphology, annexin-V and propidium iodide staining. The caspase cascade was activated as shown by the proteolytic cleavage of caspase-3 after treatment of MCF-7 cells with complex 2. Additionally, complex 2 significantly increased the expression of the Bax-to-Bcl-2 ratio to induce apoptosis. In conclusion, these results revealed that complex 2 may be a potential and promising chemotherapeutic agent to treat breast cancer.

Keywords

Cancer Apoptosis DNA cleavage Cytotoxicity 

Notes

Acknowledgments

This study was financially supported by the Pasteur Institute of Iran and the Isfahan University of Technology (IUT).

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Mona Salimi
    • 1
  • Khatereh Abdi
    • 2
  • Hirsa Mostafapour Kandelous
    • 1
  • Hassan Hadadzadeh
    • 2
  • Kayhan Azadmanesh
    • 3
  • Amir Amanzadeh
    • 4
  • Hassan Sanati
    • 4
  1. 1.Department of Physiology and PharmacologyPasteur Institute of IranTehranIran
  2. 2.Department of ChemistryIsfahan University of TechnologyIsfahanIran
  3. 3.Department of VirologyPasteur Institute of IranTehranIran
  4. 4.National Cell Bank of IranPasteur Institute of IranTehranIran

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