Author:
Dalzon Bastien,Bons Joanna,Diemer Hélène,Collin-Faure Véronique,Marie-Desvergne Caroline,Dubosson Muriel,Cianferani Sarah,Carapito Christine,Rabilloud Thierry
Abstract
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.
Funder
Agence Nationale de la Recherche
Centre National de la Recherche Scientifique
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry,Structural Biology
Cited by
12 articles.
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