In vitro and in vivo anticancer effects of two quinoline–platinum(II) complexes on human osteosarcoma models
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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 (IC50 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) Fox1nu 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.
KeywordsPlatinum Osteosarcoma Spheroids Apoptosis
SBE and IEL are members of the Research Carrer, CONICET, Argentina. JFCV and MCR have a fellowship from CONICET and ANPCyT, Argentina, respectively. We also gratefully acknowledge to Dra Ortiz Mayor from Hospital Padilla, Tucuman, Argentina, to help with the Histopathology studies. Moreover, the authors would like to thank MC. Bernal for her careful revision of the manuscript.
This work was partly supported by UNLP (11X/690), CONICET (PIP 00340), and ANPCyT (PICT 2014-2223) from Argentina and CTQ2015-64561-R from Spain.
Compliance with ethical standards
Conflict of interest
All the authors declare that they have no conflict of interest.
The animal study was conducted in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council, USA 2002. Laboratory Animals. A.A Tuffery, 1995. London: John Wiley). All efforts were made to minimize animal suffering, to decrease the number of animals used, and to utilize possible alternatives to in vivo techniques.
Research involving human participants
This article does not contain any studies with human participants performed by any of the authors.
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