TY - JOUR
T1 - Polymer “ruthenium-cyclopentadienyl” conjugates - New emerging anti-cancer drugs
AU - Moreira, Tiago
AU - Francisco, Rita
AU - Comsa, Elisabeta
AU - Duban-Deweer, Sophie
AU - Labas, Valérie
AU - Teixeira-Gomes, Ana Paula
AU - Combes-Soia, Lucie
AU - Marques, Fernanda
AU - Matos, António
AU - Favrelle, Audrey
AU - Rousseau, Cyril
AU - Zinck, Philippe
AU - Falson, Pierre
AU - Garcia, M. Helena
AU - Preto, Ana
AU - Valente, Andreia
N1 - Publisher Copyright:
© 2019 Elsevier Masson SAS
PY - 2019/4/15
Y1 - 2019/4/15
N2 - 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.
AB - 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.
KW - Cytoskeleton
KW - Polymer-metal conjugates
KW - Proteomic analysis
KW - Ruthenium organometallic compounds
UR - http://www.scopus.com/inward/record.url?scp=85062147079&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2019.02.061
DO - 10.1016/j.ejmech.2019.02.061
M3 - Article
C2 - 30826512
AN - SCOPUS:85062147079
SN - 0223-5234
VL - 168
SP - 373
EP - 384
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -
