A Proteomic View of Cellular Responses to Anticancer Quinoline-Copper Complexes.
Fiche publication
Date publication
juin 2019
Journal
Proteomes
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah, Dr CARAPITO Christine
Tous les auteurs :
Dalzon B, Bons J, Diemer H, Collin-Faure V, Marie-Desvergne C, Dubosson M, Cianferani S, Carapito C, Rabilloud T
Lien Pubmed
Résumé
Metal-containing drugs have long been used in anticancer therapies. The mechansims of action of platinum-based drugs are now well-understood, which cannot be said of drugs containing other metals, such as gold or copper. To gain further insights into such mechanisms, we used a classical proteomic approach based on two-dimensional elelctrophoresis to investigate the mechanisms of action of a hydroxyquinoline-copper complex, which shows promising anticancer activities, using the leukemic cell line RAW264.7 as the biological target. Pathway analysis of the modulated proteins highlighted changes in the ubiquitin/proteasome pathway, the mitochondrion, the cell adhesion-cytoskeleton pathway, and carbon metabolism or oxido-reduction. In line with these prteomic-derived hypotheses, targeted validation experiments showed that the hydroxyquinoline-copper complex induces a massive reduction in free glutathione and a strong alteration in the actin cytoskeleton, suggesting a multi-target action of the hydroxyquinoline-copper complex on cancer cells.
Mots clés
actin cytoskeleton, anticancer copper complex, antioxidant defense, glutathione, hydroxyquinoline copper complex, leukemic cells, proteasome, proteomics, two-dimensional electrophoresis
Référence
Proteomes. 2019 Jun 24;7(2):