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

• Main Authors: Valentina Coccè (Author), Isabella Rimoldi (Author), Giorgio Facchetti (Author), Emilio Ciusani (Author), Giulio Alessandri (Author), Lucia Signorini (Author), Francesca Sisto (Author), Aldo Giannì (Author), Francesca Paino (Author), Augusto Pessina (Author)
• Format: Book
• Published: MDPI AG, 2021-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 IC₅₀ = 3.68 ± 0.69 µM; U373-MG IC₅₀ = 11.53 ± 0.16 µM; U138-MG IC₅₀ = 8.05 ± 0.23 µM) that was higher than that observed with the clinically approved CisPt (U87-MG IC₅₀ = 7.27 + 1.80 µM; U373-MG IC₅₀ = 22.69 ± 0.05 µM; U138-MG IC₅₀ = 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.

Item Description

10.3390/pharmaceutics13122101
1999-4923