Comparative antitumor studies of organoruthenium complexes with 8-hydroxyquinolines on 2D and 3D cell models of bone, lung and breast cancer

Author:

Ruiz Maria C1,Kljun Jakob2,Turel Iztok2ORCID,Di Virgilio Ana L1,León Ignacio E1ORCID

Affiliation:

1. Inorganic Chemistry Center (CEQUINOR, CONICET), Exact School Sciences, National University of La Plata, Bv 120 1465, 1900 La Plata, Argentina

2. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia

Abstract

Abstract The purpose of this work was to screen the antitumor actions of two metal organoruthenium-8-hydroxyquinolinato (Ru-hq) complexes to find a potential novel agent for bone, lung and breast chemotherapies. We showed that ruthenium compounds (1 and 2) impaired the cell viability of human bone (MG-63), lung (A549) and breast (MCF7) cancer cells with greater selectivity and specificity than cisplatin. Besides, complexes 1 and 2 decreased proliferation, migration and invasion on cell monolayers at lower concentrations (2.5–10 μM). In addition, both compounds induced genotoxicity revealed by the micronucleus test, which led to G2/M cell cycle arrest and induced the tumor cells to undergo apoptosis. On the other hand, in multicellular 3D models (multicellular spheroids; MCS), 1 and 2 overcame CDDP presenting lower IC50 values only in MCS of lung origin. Moreover, 1 outperformed 2 in MCS of bone and breast origin. Finally, our findings revealed that both compounds inhibited the cell invasion of multicellular spheroids, showing that complex 1 exhibited the most important antimetastatic action. Taken together, these results indicate that compound 1 is an interesting candidate to be tested on in vivo models as a novel strategy for anticancer therapy.

Funder

Universidad Nacional de La Plata

Consejo Nacional de Investigaciones Científicas y Técnicas

Agencia Nacional de Promoción Científica y Tecnológica

Javna Agencija za Raziskovalno Dejavnost RS

Publisher

Oxford University Press (OUP)

Subject

Metals and Alloys,Biochemistry,Biomaterials,Biophysics,Chemistry (miscellaneous)

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