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

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 liga...

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Detalles Bibliográficos
Autores principales: Ruiz, María Carolina, Resasco, Agustina, Di Virgilio, Ana Laura, Ayala, Miguel Ángel, Cavaco, Isabel, Cabrera, Silvia, Alemán, José, León, Ignacio Esteban
Formato: Articulo
Lenguaje:Inglés
Publicado: 2019
Materias:
Química
Veterinaria
Platinum
Osteosarcoma
Spheroids
Apoptosis
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/131150
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-131150
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Química
Veterinaria
Platinum
Osteosarcoma
Spheroids
Apoptosis
spellingShingle Química
Veterinaria
Platinum
Osteosarcoma
Spheroids
Apoptosis
Ruiz, María Carolina
Resasco, Agustina
Di Virgilio, Ana Laura
Ayala, Miguel Ángel
Cavaco, Isabel
Cabrera, Silvia
Alemán, José
León, Ignacio Esteban
In vitro and in vivo anticancer effects of two quinoline–platinum(II) complexes on human osteosarcoma models
topic_facet Química
Veterinaria
Platinum
Osteosarcoma
Spheroids
Apoptosis
description 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) Fox1<sup>nu</sup> 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.
format Articulo
Articulo
author Ruiz, María Carolina
Resasco, Agustina
Di Virgilio, Ana Laura
Ayala, Miguel Ángel
Cavaco, Isabel
Cabrera, Silvia
Alemán, José
León, Ignacio Esteban
author_facet Ruiz, María Carolina
Resasco, Agustina
Di Virgilio, Ana Laura
Ayala, Miguel Ángel
Cavaco, Isabel
Cabrera, Silvia
Alemán, José
León, Ignacio Esteban
author_sort Ruiz, María Carolina
title In vitro and in vivo anticancer effects of two quinoline–platinum(II) complexes on human osteosarcoma models
title_short In vitro and in vivo anticancer effects of two quinoline–platinum(II) complexes on human osteosarcoma models
title_full In vitro and in vivo anticancer effects of two quinoline–platinum(II) complexes on human osteosarcoma models
title_fullStr In vitro and in vivo anticancer effects of two quinoline–platinum(II) complexes on human osteosarcoma models
title_full_unstemmed In vitro and in vivo anticancer effects of two quinoline–platinum(II) complexes on human osteosarcoma models
title_sort in vitro and in vivo anticancer effects of two quinoline–platinum(ii) complexes on human osteosarcoma models
publishDate 2019
url http://sedici.unlp.edu.ar/handle/10915/131150
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