Cytotoxic, pro-apoptotic, pro-oxidant, and non-genotoxic activities of a novel copper(II) complex against human cervical cancer

Toxicology. 2013 Dec 6;314(1):155-65. doi: 10.1016/j.tox.2013.08.018. Epub 2013 Sep 5.

Abstract

Cisplatin remains one of the most effective current chemotherapeutic agents; however, metal complexes synthesis has increased in order to produce new anti-neoplastic drugs with DNA binding and apoptotic activities in tumor cells and less toxicity for patients. In this study, we evaluated the cytotoxic activity of a novel copper(II) complex (LQM402) against cervical cancer cell lines and found that LQM402 exhibited selective cytotoxicity against HeLa and Ca Ski cells. FITC-annexin assay and DNA fragmentation indicated that apoptosis could be involved in HeLa cell death. Caspase 3/7 and cytochrome c analysis by immunoblotting suggest the intrinsic pathway. LQM402 is a lipid peroxidation inductor according to TBARS production. Additionally, the Ames and micronucleus tests demonstrated non-genotoxic activity for this compound in Salmonella typhimurium and CD1 mice, respectively. Therefore, LQM402 may be a promising and safe anti-cervical cancer compound.

Keywords: Apoptosis; Cervical cancer cells; Copper(II) complex; Cytotoxicity; Genotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexins
  • Apoptosis / drug effects*
  • Brain Chemistry / drug effects
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Line, Tumor
  • Coloring Agents
  • Coordination Complexes / pharmacology*
  • Coordination Complexes / toxicity
  • Copper / chemistry*
  • Cytochromes c / metabolism
  • Cytosol / metabolism
  • DNA Fragmentation / drug effects
  • Female
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate
  • HeLa Cells
  • Humans
  • In Situ Nick-End Labeling
  • Lipid Peroxidation / drug effects
  • Mice
  • Micronucleus Tests
  • Mutagenicity Tests
  • Mutagens / toxicity*
  • Oxidants / metabolism*
  • Phosphatidylserines / metabolism
  • Rats
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / metabolism
  • Tetrazolium Salts
  • Thiazoles
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • (mu4-oxo)tetra-mu4-acetate(4-hydroxy-3,5-bis(morpholinomethyl))tetracopper(II)
  • Annexins
  • Coloring Agents
  • Coordination Complexes
  • Mutagens
  • Oxidants
  • Phosphatidylserines
  • Tetrazolium Salts
  • Thiazoles
  • Copper
  • Cytochromes c
  • Caspase 3
  • Caspase 7
  • thiazolyl blue
  • Fluorescein-5-isothiocyanate