Copper(II) Complexes with Saccharinate and Glutamine as Antitumor Agents: Cytoand Genotoxicity in Human Osteosarcoma Cells

CADAVID-VARGAS J.F; LEON I.E

ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2016

1871-5206

We report herein the antitumor actions of three copper(II) complexes on MG-63 humanosteosarcoma cells. The three complexes: Cu-sac, Cu-gln and Cu-sac-gln (sac= saccharinate,gln= glutamine) caused a decline in cell viability. The half-maximal inhibitory concentration inMG-63 cells for Cu-sac-gln is 170 μM, showing the strongest antiproliferative effect. Moreover,only Cu-sac-gln caused a decrease in the mitochondrial activity from 100 μM. Our resultsindicate that the copper(II) complexes studied here produce DNA damage and suggest that therise of reactive oxygen species (ROS) is the central mechanism action. Genotoxicity studied bythe Cytokinesis-block micronucleus (MN) assay and the Single cell gel electrophoresis (cometassay) could be observed in MG-63 cells treated with Cu-sac-gln from 100 and 50 μM, respectively.Cu-sac and Cu-gln also induced DNA damage; however their effect was definitively weaker.The generation of reactive oxygen species increased from 50 μM of Cu-sac-gln and Cu-sac andonly from 250 μM of Cu-gln, as well as a reduction of the GSH/GSSG ratio from 50 μM. When cells were treated withseveral concentrations of the complexes in addition to a combination of 50 μM of vitamin C plus 50 μM of vitamin E,a total recovery in cell survival was obtained for Cu-gln in the whole range of tested concentrations while only a partialviability recovery was obtained from 250 μM of Cu-sac and Cu-sac-gln. Overall, our results point to a differentialcyto- and genotoxicity of the three copper(II) complexes and demonstrate that the complexation with both ligandsconfers the most potent antitumor action in human osteosarcoma cells.