title: Polyoxometalates as antitumor agents: Bioactivity of a new polyoxometalate with copper on a human osteosarcoma model.
abstract: Polyoxometalates (POMs) are early transition metal oxygen anion clusters. They display interesting biological effects mainly related to their antiviral and antitumor properties. On the other hand, copper compounds also show different biological and pharmacological effects in cell culture and in animal models. We report herein for the first time, a detailed study of the mechanisms of action of a copper(II) compound of the group of HPOMs with the formula K7Na3[Cu4(H2O)2(PW9034)2]20H2O (PW9Cu), in a model of human osteosarcoma derived cell line, MG-63. The compound inhibited selectively the viability of the osteosarcoma cells in the range of 25-100μM (p<0.01). Besides, we have clearly shown a more deleterious action of PW9Cu on tumor osteoblasts than in normal cells. Cytotoxicity studies also showed deleterious effects for PW9Cu. The increment of reactive oxygen species (ROS) and the decrease of the GSH/GSSG ratio were involved in the antiproliferative effects of PW9Cu. Moreover, the compound caused cell cycle arrest in G2 phase, triggering apoptosis as determined by flow cytometry. As a whole, these results showed the main mechanisms of the deleterious effects of PW9Cu in the osteosarcoma cell line MG-63, demonstrating that this compound is a promissory agent for cancer treatments.
authors.affiliation: Centro de Química Inorgánica (CONICET-UNLP), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina.
authors.forename: I E
authors.initials: IE
authors.lastname: León
authors.affiliation: Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, 11400, Uruguay.
authors.forename: V
authors.initials: V
authors.lastname: Porro
authors.affiliation: Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, 11400, Uruguay.
authors.forename: S
authors.initials: S
authors.lastname: Astrada
authors.affiliation: Centro de Investigación y Desarrollo en Ciencias Aplicadas CINDECA, La Plata, Argentina.
authors.forename: M G
authors.initials: MG
authors.lastname: Egusquiza
authors.affiliation: Centro de Investigación y Desarrollo en Ciencias Aplicadas CINDECA, La Plata, Argentina.
authors.forename: C I
authors.initials: CI
authors.lastname: Cabello
authors.affiliation: Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, 11400, Uruguay.
authors.forename: M
authors.initials: M
authors.lastname: Bollati-Fogolin
authors.affiliation: Centro de Química Inorgánica (CONICET-UNLP), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina. Electronic address: etcheverry@biol.unlp.edu.ar.
authors.forename: S B
authors.initials: SB
authors.lastname: Etcheverry
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D053938:DNA Fragmentation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000737:chemistry / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism; D017973:Tungsten Compounds / Q000737:chemistry / Q000494:pharmacology*; D000099294:Polyoxometalates
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003300:Copper; D005978:Glutathione; D010087:Oxides; D010718:Phosphatidylserines; D017973:Tungsten Compounds; C102296:polyoxometalate I; D000099294:Polyoxometalates
keywords: Anticancer drug; Copper; MG-63 human osteosarcoma cells; Mechanisms of action; Polyoxometalates