Title :

Polymer “ruthenium-cyclopentadienyl” conjugates - New emerging anti-cancer drugs

Author(s) :

Moreira, Tiago [Auteur]
Centre of Molecular and Environmental Biology - CBMA (Braga, Portugal)
Faculdade de Ciências [Lisboa]
Francisco, Rita [Auteur]
Centre of Molecular and Environmental Biology - CBMA (Braga, Portugal)
Faculdade de Ciências [Lisboa]
Comsa, Elisabeta [Auteur]
Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry [MMSB]
Duban-Deweer, Sophie [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Labas, Valérie [Auteur]
Université de Tours [UT]
Teixeira-Gomes, Ana-Paula [Auteur]
Université de Tours [UT]
Combes-Soia, Lucie [Auteur]
Université de Tours [UT]
Marques, Fernanda [Auteur]
University of Lisboa
Matos, António [Auteur]
Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento em Lisboa [INESC-ID]
Huret, Audrey [Auteur]
Unité de Catalyse et Chimie du Solide - UMR 8181 [UCCS]
Rousseau, Cyril [Auteur]
Unité de Catalyse et Chimie du Solide - UMR 8181 [UCCS]
Zinck, Philippe [Auteur]
Unité de Catalyse et Chimie du Solide - UMR 8181 [UCCS]
Falson, Pierre [Auteur]
Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry [MMSB]
Garcia, M. Helena [Auteur]
University of Lisboa
Preto, Ana [Auteur]
Centre of Molecular and Environmental Biology - CBMA (Braga, Portugal)
Valente, Andreia [Auteur]
University of Lisboa

Journal title :

European journal of medicinal chemistry

Volume number :

168

Pages :

373-384

Publication date :

2019

English keyword(s) :

Ruthenium organometallic compounds
Polymer-metal conjugates
Proteomic analysis
Cytoskeleton

HAL domain(s) :

Chimie/Catalyse

English abstract : [en]

In this work, we aimed to understand the biological activity and the mechanism of action of three polymer-‘ruthenium-cyclopentadienyl’ conjugates (RuPMC) and a low molecular weight parental compound (Ru1) in cancer cells. ...
Show more >In this work, we aimed to understand the biological activity and the mechanism of action of three polymer-‘ruthenium-cyclopentadienyl’ conjugates (RuPMC) and a low molecular weight parental compound (Ru1) in cancer cells. Several biological assays were performed in ovarian (A2780) and breast (MCF7, MDA-MB-231) human cancer derived cell lines as well as in A2780cis, a cisplatin resistant cancer cell line. Our results show that all compounds have high activity towards cancer cells with low IC50 values in the micromolar range. We observed that all Ru-PMC compounds are mainly found inside the cells, in contrast with the parental low molecular weight compound Ru1 that was mainly found at the membrane. All compounds induced mitochondrial alterations. PMC3 and Ru1 caused F-actin cytoskeleton morphology changes and reduced the clonogenic ability of the cells. The conjugate PMC3 induced apoptosis at low concentrations comparing to cisplatin and could overcame the platinum resistance of A2780cis cancer cells. A proteomic analysis showed that these compounds induce alterations in several cellular proteins which are related to the phenotypic disorders induced by them. Our results suggest that PMC3 is foreseen as a lead candidate to future studies and acting through a different mechanism of action than cisplatin. Here we established the potential of these Ru compounds as new metallodrugs for cancer chemotherapy.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

ENSCL
CNRS
Centrale Lille
Univ. Artois
Université de Lille

Collections :

• Unité de Catalyse et Chimie du Solide (UCCS) - UMR 8181

Research team(s) :

Catalyse et chimie supramoléculaire (CASU)
Catalyse et synthèse éco-compatible (CASECO)

Submission date :

2019-09-25T15:07:16Z
2020-12-03T12:55:27Z
2021-05-25T07:06:32Z