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.
Highlights
Metal-containing drugs, i.e., metal-organic complexes, known as metallodrugs, have been used to combat cancer for quite a long time
Their binding to proteins have been extensively studied, they suggest that different ruthenium metallodrugs bind to different proteins [13]
It has been demonstrated that in most cases, the the different proteins contained in a single spot are present in very different amounts, and that the different proteins contained in a single spot are present in very different amounts, and that the variations detected via image analysis of 2D gels impact the most abundant protein in the spot [77]
Summary
Metal-containing drugs, i.e., metal-organic complexes, known as metallodrugs, have been used to combat cancer for quite a long time. Because of the side effects of these drugs and of the emergence of resistances, other metal complexes have been investigated as anticancer agents. Various metals such as gold [4,5], copper [6,7], zinc [8] or ruthenium [9,10,11]. Various mechanisms of actions have been proposed for these non-platinum metallodrugs. For ruthenium complexes, their binding to proteins have been extensively studied, they suggest that different ruthenium metallodrugs bind to (and may inhibit) different proteins [13]
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