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.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Annexins
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Apoptosis / drug effects*
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Brain Chemistry / drug effects
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Caspase 3 / metabolism
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Caspase 7 / metabolism
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Cell Line, Tumor
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Coloring Agents
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Coordination Complexes / pharmacology*
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Coordination Complexes / toxicity
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Copper / chemistry*
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Cytochromes c / metabolism
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Cytosol / metabolism
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DNA Fragmentation / drug effects
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Female
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Flow Cytometry
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Fluorescein-5-isothiocyanate
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HeLa Cells
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Humans
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In Situ Nick-End Labeling
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Lipid Peroxidation / drug effects
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Mice
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Micronucleus Tests
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Mutagenicity Tests
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Mutagens / toxicity*
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Oxidants / metabolism*
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Phosphatidylserines / metabolism
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Rats
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Salmonella typhimurium / drug effects
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Salmonella typhimurium / metabolism
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Tetrazolium Salts
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Thiazoles
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Uterine Cervical Neoplasms / drug therapy*
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Uterine Cervical Neoplasms / metabolism
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Uterine Cervical Neoplasms / pathology
Substances
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(mu4-oxo)tetra-mu4-acetate(4-hydroxy-3,5-bis(morpholinomethyl))tetracopper(II)
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Annexins
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Coloring Agents
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Coordination Complexes
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Mutagens
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Oxidants
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Phosphatidylserines
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Tetrazolium Salts
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Thiazoles
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Copper
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Cytochromes c
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Caspase 3
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Caspase 7
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thiazolyl blue
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Fluorescein-5-isothiocyanate