In vitro anticancer activity of two novel Ru hidroxiquinolines compounds against 2d and 3d cell models.

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

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

The development of ruthenium complex has shown to be very potential as anti-tumor agents. These compounds have high specificity for cancer cells.The aim of this project is to evaluate the antitumoral activity of two novel Ruthenium hidroxiquinoline complexes, HQRuBr (4) and HQRuBr2 (5), in cancer monolayer and spheroids models. The cytotoxic assays were carried out on a panel of human cancer cell lines including MG-63 (osteosarcoma), A549 (lung), MCF7(breast), MDA-MB-231(breast) and one normal cell line L929 (mouse fribroblast), using MTT and alamar blue assay. The Ru compounds decrease cell viability in all cells lines tested, MG-63 (IC50 complex 4 13,6 µM and complex 5 10,4 µM), A549 (IC50 Complex 4: 52,9 µM and Complex 5: 26,7 µM), MCF7 (IC50 complex 4: 46.1 µM and complex 5: 20.7 µM), MDA-MB-231 (IC50 complex 4: 38.2 µM and complex 5: 15.8 µM) and L929 (IC50 complex 4: 43,5 µM complex 5: 26.7 µM) (p˂0.001). Furthermore, the wound healing assay showed Ru complexes decline MG-63 cells migrations, nearly a 50% and single cell lamellipodium formation diminished too. The genototoxic activity on MG-63 cell line was determinate using micronucleus and comet assay; these processes expose increased tail moment and the formation of micronucleus in a concentration range of 2.5 to 10 µM (p˂0.001). The cell cycle was analyzed by flow cytometry, showing that compound 4 and 5 arrest the cell cycle in G1 phase.Finally, both compounds diminished the cell viability on spheroids (MG-63, A549 and MCF-7) affecting the volume and spherical shape (p˂0.005).In summary, these two Ru complexes show antitumoral activity, both caused cytotoxicity and genotoxicity in all tumoral cell lines in a concentration dependent manner but the compound 5 has a stronger activity than compound 4. Therefore, our results show that compound 5 is the most interesting candidate for potential antitumor uses, and it would be interesting to test this complex in further in vivo studies for cancer treatments.