Cyto- and genotoxicity of a ruthenium-clioquinol complex against 2D and 3D human osteosarcoma models

RUIZ, M.C.; CADAVID VARGAS J.F.; KLJUN, J; DI VIRGILIO A.L.; TURREL I; LEON, I.E; ETCHEVERRY S.B.

Congreso; X Congreso ALAMCTA; 2016

As of the use of cisplatin as an anti-tumor drug, the development of ruthenium complex has shown to be very potential as anti-tumor agents. These compounds have high specificity for cancer cells, with very low side effects. Clioquinol is an inducer of cell death and it can form stable complexes.The aim of this project is to determine the cyto- and genotoxic activity of the Ru (Cym-CQCl) in cellular monolayers and in spherical 3D models using MG-63 cells.The cytotoxicity of the compound was evaluated with MTT assay. Concerning the genotoxic potential, this was evaluated using the comet and micronucleus techniques. Besides it was evaluated the nuclease activity of the complex as another genotoxicity parameter. Besides, the antitumor properties of the Ru compound on 3D model were performed through the circularity measure and cell viability using acid phosphatase assay.The MTT assay demonstrates that the complex impairs the metabolism of mitochondria. The compound decrease the cell viability in a 50% after 24 hours of incubation with 25 µM and at 50 µM the cell viability was less than 40%. The data also show that CQ decreased the viability around 20%, proving the biological effects of complexing this ligand with ruthenium.The complex exhibited nuclease activity toward pA1.The genotoxic process was further shown through increased tail moment and the formation of micronucleus in a concentration range of 2.5 µM to 10 µM. It be assumed that the compound shows the ability to induce DNA damage in these cells. Moreover, the spheroid diminished their spherical shape, and the viability of these cells appeared to be 30% less. The results imply that the complex has a potent anti?tumor activity in this model, as it reduced the size of the spheroid affecting the cell viability.