title: Cytotoxic, pro-apoptotic, pro-oxidant, and non-genotoxic activities of a novel copper(II) complex against human cervical cancer.
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.
authors.affiliation: Laboratorio de Biología Celular y Productos Naturales, Escuela Nacional de Medicina y Homeopatía-IPN, Guillermo Massieu Helguera 239, Fracc. La Escalera, Ticoman, D.F. 07320, Mexico.
authors.forename: Susana E
authors.initials: SE
authors.lastname: Frías González
authors.forename: Enrique
authors.initials: E
authors.lastname: Angeles Anguiano
authors.forename: Alberto
authors.initials: A
authors.lastname: Mendoza Herrera
authors.forename: Daniel
authors.initials: D
authors.lastname: Escutia Calzada
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ordaz Pichardo
mesh_terms: D000818:Animals; D017302:Annexins; D017209:Apoptosis / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D004396:Coloring Agents; D056831:Coordination Complexes / Q000494:pharmacology* / Q000633:toxicity; D003300:Copper / Q000737:chemistry*; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D016877:Oxidants / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C585577:(mu4-oxo)tetra-mu4-acetate(4-hydroxy-3,5-bis(morpholinomethyl))tetracopper(II); D017302:Annexins; D004396:Coloring Agents; D056831:Coordination Complexes; D009153:Mutagens; D016877:Oxidants; D010718:Phosphatidylserines; D013778:Tetrazolium Salts; D013844:Thiazoles; D003300:Copper; D045304:Cytochromes c; D053148:Caspase 3; D053179:Caspase 7; C022616:thiazolyl blue; D016650:Fluorescein-5-isothiocyanate
keywords: Apoptosis; Cervical cancer cells; Copper(II) complex; Cytotoxicity; Genotoxicity