79010 20200716101501.0 doi 10.1155/2019/3061607 sideral 111495 ART-2019-111495 eng Buric, S.S. Modulation of antioxidant potential with coenzyme Q10 suppressed invasion of temozolomide-resistant rat glioma in vitro and in vivo 2019 Access copy available to the general public Unrestricted The main reasons for the inefficiency of standard glioblastoma (GBM) therapy are the occurrence of chemoresistance and the invasion of GBM cells into surrounding brain tissues. New therapeutic approaches obstructing these processes may provide substantial survival improvements. The purpose of this study was to assess the potential of lipophilic antioxidant coenzyme Q10 (CoQ10) as a scavenger of reactive oxygen species (ROS) to increase sensitivity to temozolomide (TMZ) and suppress glioma cell invasion. To that end, we used a previously established TMZ-resistant RC6 rat glioma cell line, characterized by increased production of ROS, altered antioxidative capacity, and high invasion potential. CoQ10 in combination with TMZ exerted a synergistic antiproliferative effect. These results were confirmed in a 3D model of microfluidic devices showing that the CoQ10 and TMZ combination is more cytotoxic to RC6 cells than TMZ monotherapy. In addition, cotreatment with TMZ increased expression of mitochondrial antioxidant enzymes in RC6 cells. The anti-invasive potential of the combined treatment was shown by gelatin degradation, Matrigel invasion, and 3D spheroid invasion assays as well as in animal models. Inhibition of MMP9 gene expression as well as decreased N-cadherin and vimentin protein expression implied that CoQ10 can suppress invasiveness and the epithelial to mesenchymal transition in RC6 cells. Therefore, our data provide evidences in favor of CoQ10 supplementation to standard GBM treatment due to its potential to inhibit GBM invasion through modulation of the antioxidant capacity. info:eu-repo/grantAgreement/ES/MINECO-FEDER/BIO2016-79092-R info:eu-repo/grantAgreement/ES/MINECO-FEDER/DPI2015-65401-C3-1-R info:eu-repo/grantAgreement/ES/MINECO-FEDER/MTM2015-71200-R info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.076 2019 CELL BIOLOGY 56 / 195 = 0.287 2019 Q2 T1 1.394 2019 Biochemistry 2019 Q1 Medicine (miscellaneous) 2019 Q1 Cell Biology 2019 Q2 Aging 2019 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Podolski-Renic, A. Dinic, J. Stankovic, T. Jovanovic, M. Hadžic, S. (orcid)0000-0002-9414-1845 Ayuso, J.M. (orcid)0000-0003-3660-8651 Virumbrales-Muñoz, M. (orcid)0000-0001-5376-4440 Fernández, L.J. Universidad de Zaragoza (orcid)0000-0003-2410-5678 Ochoa, I. Universidad de Zaragoza Pérez-García, V.M. Pešic, M. 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 5004 605 Universidad de Zaragoza Dpto. Ingeniería Mecánica Área Mec.Med.Cont. y Teor.Est. 2019 (2019), 3061607 [14 pp] Oxidative Medicine and Cellular Longevity Oxidative Medicine and Cellular Longevity 1942-0900 809166 http://zaguan.unizar.es/record/79010/files/texto_completo.pdf Versión publicada 88597 http://zaguan.unizar.es/record/79010/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:79010 articulos driver 2020-07-16-09:13:02 ARTICLE