Unpublished conference/Abstract (Scientific congresses and symposiums)
Modulatory effects of Ruthenium (II)-based complexes on oxidative stress induced by activated HL60 cells and Neutrophils
Mouithys-Mickalad, Ange; Collienne, Simon; Franck, Thierry et al.
201523rd Benelux EPR Society Meeting
 

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Keywords :
EPR; Ruthenium; PMN; HL-60 cells; complexes
Abstract :
[en] There is a growing interest on the use of metal-based chemotherapeutic agents to fight different types of cancers [1]. The most used family of the organometallic compounds is platinum derivatives whose Cisplatin (CisPt) is the lead compound used for the treatment of various cancers including lung, testis, gastric, breast, etc. Nevertheless, beside its recognized therapeutic effects, side effects such as gastric toxicity and acute kidney failure were observed during the treatment, limiting its clinical use. Other compounds are currently studied and among them, Ruthenium (Ru) complexes have gained more importance for their less toxicity and lower aggressive effect on healthy tissues than CisPt. Ru-complexes are also more resorbed and excreted [2]. Numerous studies focused on the mechanisms of action of Ruthenium compounds to fight cancer, including antioxidant or pro-oxidant activity. During inflammation, activation and infiltration of neutrophils contribute to oxidant stress playing a crucial role in tumor development. Likewise, the degranulation of neutrophil causes the release of myeloperoxidase (MPO) which reacts with H2O2 to catalyze redox reactions. A therapeutic target to control inflammation is the modulation of oxidant enzymes and cells involved in radical species production and redox reactions. Because Ruthenium compounds can easily enter into cancer cells, a series of Ru(II)-complexes newly synthesized were used for this purpose. They were first tested for their radical scavenging activities using ABTS and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays. Amongst them, compound 1 (LD0436) and compound 2 (LD04037) were then studied for their ability to modulate the reactive oxygen species (ROS) production by inflammatory cells like human promyelocytic leukemia cell line (HL 60) and neutrophils (PMN) using fluorescence, chemiluminescence (CL) and electron spin resonance ESR techniques. The toxicity of those Ru-complexes against HL-60 and neutrophils was checked using Trypan blue exclusion assay. Altogether, CL and ESR findings indicate that both complexes 1 (LD0436) and 2 (LD0437) exhibit a dose-dependent inhibitory activity compared to CisPt, gallic acid, curcumin and quercetin, which were taken as reference molecules in the different systems investigated. Similarly, the tested complexes also display an antioxidant profile on the substrate oxidation catalyzed by peroxidase such as MPO mainly involved in acute and chronic inflammatory situations. 1: (RuCl(p-Cymen)(S2C.IDip)]+(PF6)-], 2: (RuCl(p-Cymen)(S2C.Icy)]+(PF6)-] References: 1. Ceresa C, Brawin A, Cavaletti G, Trinidad A et al., (2014) Current Medicinal Chemistry 20(21), 2237-2265. 2. Liu, Y, Zhang X, Zhang R, et al., (2011) European Journal of Inorganic Chemistry. 1974-1980.
Research center :
CORD - Centre de l'Oxygène, Recherche et Développement - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Mouithys-Mickalad, Ange ;  Université de Liège > Centre de l'oxygène : Recherche et développement (C.O.R.D.)
Collienne, Simon  ;  Université de Liège > Département de physique > Spectroscopie biomédicale
Franck, Thierry  ;  Université de Liège > Centre de l'oxygène : Recherche et développement (C.O.R.D.)
Delaude, Lionel  ;  Université de Liège > Département de chimie (sciences) > Chimie organométallique et catalyse homogène
Hoebeke, Maryse  ;  Université de Liège > Département de physique > Spectroscopie biomédicale
Serteyn, Didier  ;  Université de Liège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Anesthésiologie gén. et pathologie chirurg. des grds animaux
Vaesen, Fanny
Moerman, Jerôme
Language :
English
Title :
Modulatory effects of Ruthenium (II)-based complexes on oxidative stress induced by activated HL60 cells and Neutrophils
Publication date :
22 May 2015
Number of pages :
1
Event name :
23rd Benelux EPR Society Meeting
Event organizer :
Henk Vrielinck and Freddy Callens, Ghent University
Event place :
Ghent, Belgium
Event date :
22 mai 2015
By request :
Yes
Audience :
International
Name of the research project :
Etude des propriétés biologiques des complexes à base de ruthénium
Funders :
ULg - University of Liège [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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