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A Proteomic View of Cellular Responses to Anticancer Quinoline-Copper Complexes

1
Chemistry and Biology of Metals, Univ. Grenoble Alpes, CNRS UMR5249, CEA, IRIG,CBM, F-38054 Grenoble, France
2
Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), Université de Strasbourg, CNRS, IPHC UMR 7178, 67000 Strasbourg, France
3
Nanosafety Platform, Medical Biology Laboratory (LBM), Univ. Grenoble-Alpes, CEA, 17 rue des Martyrs, F-38054 Grenoble, France
*
Author to whom correspondence should be addressed.
Proteomes 2019, 7(2), 26; https://doi.org/10.3390/proteomes7020026
Received: 28 May 2019 / Revised: 18 June 2019 / Accepted: 21 June 2019 / Published: 24 June 2019
(This article belongs to the Special Issue Top-down Proteomics: In Memory of Dr. Alfred Yergey)
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. View Full-Text
Keywords: anticancer copper complex; hydroxyquinoline copper complex; leukemic cells; proteomics; two-dimensional electrophoresis; proteasome; glutathione; actin cytoskeleton; antioxidant defense anticancer copper complex; hydroxyquinoline copper complex; leukemic cells; proteomics; two-dimensional electrophoresis; proteasome; glutathione; actin cytoskeleton; antioxidant defense
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Dalzon, B.; Bons, J.; Diemer, H.; Collin-Faure, V.; Marie-Desvergne, C.; Dubosson, M.; Cianferani, S.; Carapito, C.; Rabilloud, T. A Proteomic View of Cellular Responses to Anticancer Quinoline-Copper Complexes. Proteomes 2019, 7, 26.

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