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In Vitro Activity of Monofunctional Pt-II Complex Based on 8-Aminoquinoline against Human Glioblastoma

A new cationic Pt(II) complex bearing 8-aminoquinoline as chelating ligand (called Pt-8AQ) was evaluated against two human carcinomas, one mesothelioma, and three glioblastoma cell lines. The in vitro comparison to the clinically approved CisPt showed a minor activity of Pt-8AQ against carcinoma and...

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Autores principales: Coccè, Valentina, Rimoldi, Isabella, Facchetti, Giorgio, Ciusani, Emilio, Alessandri, Giulio, Signorini, Lucia, Sisto, Francesca, Giannì, Aldo, Paino, Francesca, Pessina, Augusto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704014/
https://www.ncbi.nlm.nih.gov/pubmed/34959382
http://dx.doi.org/10.3390/pharmaceutics13122101
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author Coccè, Valentina
Rimoldi, Isabella
Facchetti, Giorgio
Ciusani, Emilio
Alessandri, Giulio
Signorini, Lucia
Sisto, Francesca
Giannì, Aldo
Paino, Francesca
Pessina, Augusto
author_facet Coccè, Valentina
Rimoldi, Isabella
Facchetti, Giorgio
Ciusani, Emilio
Alessandri, Giulio
Signorini, Lucia
Sisto, Francesca
Giannì, Aldo
Paino, Francesca
Pessina, Augusto
author_sort Coccè, Valentina
collection PubMed
description A new cationic Pt(II) complex bearing 8-aminoquinoline as chelating ligand (called Pt-8AQ) was evaluated against two human carcinomas, one mesothelioma, and three glioblastoma cell lines. The in vitro comparison to the clinically approved CisPt showed a minor activity of Pt-8AQ against carcinoma and mesothelioma, whereas a significant activity of Pt-8AQ was observed on the proliferation of the three glioblastoma cell lines (U87-MG IC(50) = 3.68 ± 0.69 µM; U373-MG IC(50) = 11.53 ± 0.16 µM; U138-MG IC(50) = 8.05 ± 0.23 µM) that was higher than that observed with the clinically approved CisPt (U87-MG IC(50) = 7.27 + 1.80 µM; U373-MG IC(50) = 22.69 ± 0.05 µM; U138-MG IC(50) = 32.1 ± 4.44 µM). Cell cycle analysis proved that Pt-8AQ significantly affected the cell cycle pattern by increasing the apoptotic cells represented by the sub G0/G1 region related with a downregulation of p53 and Bcl-2. Moreover, an NMR investigation of Pt-8AQ interaction with 9-EtG, GSH, and Mets7 excluded DNA as the main target, suggesting a novel mechanism of action. Our study demonstrated the high stability of Pt-8AQ after incubation at 37 °C and a significant antineoplastic activity on glioblastomas. These features also make Pt-8AQ a good candidate for developing a new selective advanced cell chemotherapy approach in combination with MSCs.
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spelling pubmed-87040142021-12-25 In Vitro Activity of Monofunctional Pt-II Complex Based on 8-Aminoquinoline against Human Glioblastoma Coccè, Valentina Rimoldi, Isabella Facchetti, Giorgio Ciusani, Emilio Alessandri, Giulio Signorini, Lucia Sisto, Francesca Giannì, Aldo Paino, Francesca Pessina, Augusto Pharmaceutics Article A new cationic Pt(II) complex bearing 8-aminoquinoline as chelating ligand (called Pt-8AQ) was evaluated against two human carcinomas, one mesothelioma, and three glioblastoma cell lines. The in vitro comparison to the clinically approved CisPt showed a minor activity of Pt-8AQ against carcinoma and mesothelioma, whereas a significant activity of Pt-8AQ was observed on the proliferation of the three glioblastoma cell lines (U87-MG IC(50) = 3.68 ± 0.69 µM; U373-MG IC(50) = 11.53 ± 0.16 µM; U138-MG IC(50) = 8.05 ± 0.23 µM) that was higher than that observed with the clinically approved CisPt (U87-MG IC(50) = 7.27 + 1.80 µM; U373-MG IC(50) = 22.69 ± 0.05 µM; U138-MG IC(50) = 32.1 ± 4.44 µM). Cell cycle analysis proved that Pt-8AQ significantly affected the cell cycle pattern by increasing the apoptotic cells represented by the sub G0/G1 region related with a downregulation of p53 and Bcl-2. Moreover, an NMR investigation of Pt-8AQ interaction with 9-EtG, GSH, and Mets7 excluded DNA as the main target, suggesting a novel mechanism of action. Our study demonstrated the high stability of Pt-8AQ after incubation at 37 °C and a significant antineoplastic activity on glioblastomas. These features also make Pt-8AQ a good candidate for developing a new selective advanced cell chemotherapy approach in combination with MSCs. MDPI 2021-12-07 /pmc/articles/PMC8704014/ /pubmed/34959382 http://dx.doi.org/10.3390/pharmaceutics13122101 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Coccè, Valentina
Rimoldi, Isabella
Facchetti, Giorgio
Ciusani, Emilio
Alessandri, Giulio
Signorini, Lucia
Sisto, Francesca
Giannì, Aldo
Paino, Francesca
Pessina, Augusto
In Vitro Activity of Monofunctional Pt-II Complex Based on 8-Aminoquinoline against Human Glioblastoma
title In Vitro Activity of Monofunctional Pt-II Complex Based on 8-Aminoquinoline against Human Glioblastoma
title_full In Vitro Activity of Monofunctional Pt-II Complex Based on 8-Aminoquinoline against Human Glioblastoma
title_fullStr In Vitro Activity of Monofunctional Pt-II Complex Based on 8-Aminoquinoline against Human Glioblastoma
title_full_unstemmed In Vitro Activity of Monofunctional Pt-II Complex Based on 8-Aminoquinoline against Human Glioblastoma
title_short In Vitro Activity of Monofunctional Pt-II Complex Based on 8-Aminoquinoline against Human Glioblastoma
title_sort in vitro activity of monofunctional pt-ii complex based on 8-aminoquinoline against human glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704014/
https://www.ncbi.nlm.nih.gov/pubmed/34959382
http://dx.doi.org/10.3390/pharmaceutics13122101
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