In vitro and in vivo anticancer effects of two quinoline–platinum(II) complexes on human osteosarcoma models

Abstract

Platinum-based drugs, mainly cisplatin, are used for the treatment of several solid tumors such as OS. However, cisplatin treatment often results in the development of chemoresistance, leading therapeutic failure. We have previously reported that platinum complexes containing 8-hydroxyquinoline ligands have good antitumor activity against different cancer cell lines and with a different and better cytotoxic profile than cisplatin. Here, the anticancer properties of two different quinoline-platinum complexes [Pt(Cl) 2 (quinoline)(dmso)] (1) [PtCl(8-O-quinoline)(dmso)] (2) on in vitro (2D and 3D) and in vivo models (xenograft tumor of human osteosarcoma in mice) are presented. In this order, [PtCl(8-O-quinoline)(dmso)] (2) impaired cell viability to have a more pronounced antitumor effect than cisplatin on MG-63 osteosarcoma cells (IC 50 4 µM vs. 39 µM). Besides, [PtCl(8-O-quinoline)(dmso)] (2) increased ROS production in a dose-manner response and this compound induced early and late apoptotic fractions of human osteosarcoma cells. Finally, [PtCl(8-O-quinoline)(dmso)] (2) decreased the cell viability of multicellular spheroids and reduced the tumor volume on athymic nude mice N:NIH(S) Fox1 nu without inducing side effects. In this way, [PtCl(8-O-quinoline)(dmso)] (2) did not alter the normal cytoarchitecture of liver and kidney and the blood biomarkers (GPT, GOT, uremia, and creatinine) did not suffer modifications. Taken together, our data indicate that these compounds showed a better anticancer performance than cisplatin on in vitro and in vivo studies. These results showed the importance of chelation in the antitumor properties, suggesting that the [PtCl(8-O-quinoline)(dmso)] (2) might be a promising agent for the treatment of human osteosarcoma tumors resistant to cisplatin.

A 3D Printed Bone Tissue Engineering Scaffold Composed of Alginate Dialdehyde‐Gelatine Reinforced by Lysozyme Loaded Cerium Doped Mesoporous Silica‐Calcia Nanoparticles

“…ADA‐GEL has been shown to have a non‐harmful effect on MG63 cells, [ 22 ] therefore less viability of these cells adjacent to the nanocomposite hydrogel scaffold can solely be attributed to Lys. It is worthy to note that MG63 osteosarcoma cells have been considered as a cancer cell model to monitor the anticancer properties of different compounds such as quinoline‐platinium complex, [ 64 ] doxorubicin hydrochloride, [ 65 ] lactoferrin, [ 66 ] among others. Anticancer effects of Lys have been proven by other research groups and have been attributed to the increased production of reactive oxygen species (ROS) by this enzyme.…”

Evaluation of the Anticancer Activities of Novel Transition Metal Complexes with Berenil and Nitroimidazole

“…Therefore much research aims at the synthesis of new complexes directed at different targets. The presence of a less labile ligand in the structure of new generation platinum drugs may contribute to the lower toxicity of these compounds, especially neuro- and nephron- toxicity, while maintaining the same, and in some cases greater, antitumor activity [ 17 , 18 ]. The compounds synthesized by our team seem to confirm this thesis.…”

Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway

“…The data was averaged in six replicates, and each experiment was repeated for three times. In initial dose–response study, different concentrations of cisplatin and zey were respectively based on relevant references (Ruiz et al, 2019; Yong et al, 2018) and our previous studies (L. Zhang et al, 2015).…”