In vitro anticancer activity of two novel Ru Hidroxiquinolines compounds against 2D and 3D cells models

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

Congreso; Reunión Conjunta de BIOCIENCIAS 2017; 2017

The development of ruthenium complex has shown to be very potentialas anti-tumor agents.Thesecompoundshavehighspecificityforcancer cells.The aim of this project is to evaluate the antitumoral activity oftwo novel Ruthenium hidroxiquinoline complexes, HQRuBr (4) andHQRuBr(5), in cancer monolayer and spheroids models. The cytotoxicassays were carried out on a panel of human cancer cell linesincludingMG-63(osteosarcoma),A549(lung),MCF7(breast),MDAMB-231(breast)andone normal celllineL929(mousefribroblast),usingMTTand alamar blue assay.TheRu compounds decreasecellviability in all cells lines tested, MG-63 (IC2 complex 4 13,6µM and complex 5 10,4 µM), A549 (IC5050 Complex 4: 52,9 µM andComplex 5: 26,7 µM), MCF7 (IC complex 4: 46.1 µM and complex5: 20.7 µM), MDA-MB-231 (IC5050 complex 4: 38.2 µM and complex5: 15.8 µM) and L929 (IC complex 4: 43,5 µM complex 5: 26.7µM) (p˂0.001). Furthermore, the wound healing assay showed Rucomplexes decline MG-63 cells migrations, nearly a 50% and singlecell lamellipodium formation diminished too. The genototoxic activityon MG-63 cell line was determinate using micronucleus and cometassay;theseprocesses expose increased tail moment and theformationofmicronucleusinaconcentrationrangeof2.5to10µM(p˂0.001). The cell cycle was analyzed by flow cytometry, showingthat compound 4 and 5 arrest the cell cycle in G1 phase.50Finally, 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 linesin a concentration dependent manner but the compound 5 has astronger activity than compound 4. Therefore, our results show thatcompound 5 is the most interesting candidate for potential antitumoruses, and it would be interesting to test this complex in further in vivostudies for cancer treatments