000079010 001__ 79010
000079010 005__ 20200716101501.0
000079010 0247_ $$2doi$$a10.1155/2019/3061607
000079010 0248_ $$2sideral$$a111495
000079010 037__ $$aART-2019-111495
000079010 041__ $$aeng
000079010 100__ $$aBuric, S.S.
000079010 245__ $$aModulation of antioxidant potential with coenzyme Q10 suppressed invasion of temozolomide-resistant rat glioma in vitro and in vivo
000079010 260__ $$c2019
000079010 5060_ $$aAccess copy available to the general public$$fUnrestricted
000079010 5203_ $$aThe 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.
000079010 536__ $$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/BIO2016-79092-R$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/DPI2015-65401-C3-1-R$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/MTM2015-71200-R
000079010 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000079010 590__ $$a5.076$$b2019
000079010 591__ $$aCELL BIOLOGY$$b56 / 195 = 0.287$$c2019$$dQ2$$eT1
000079010 592__ $$a1.394$$b2019
000079010 593__ $$aBiochemistry$$c2019$$dQ1
000079010 593__ $$aMedicine (miscellaneous)$$c2019$$dQ1
000079010 593__ $$aCell Biology$$c2019$$dQ2
000079010 593__ $$aAging$$c2019$$dQ2
000079010 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000079010 700__ $$aPodolski-Renic, A.
000079010 700__ $$aDinic, J.
000079010 700__ $$aStankovic, T.
000079010 700__ $$aJovanovic, M.
000079010 700__ $$aHadžic, S.
000079010 700__ $$0(orcid)0000-0002-9414-1845$$aAyuso, J.M.
000079010 700__ $$0(orcid)0000-0003-3660-8651$$aVirumbrales-Muñoz, M.
000079010 700__ $$0(orcid)0000-0001-5376-4440$$aFernández, L.J.$$uUniversidad de Zaragoza
000079010 700__ $$0(orcid)0000-0003-2410-5678$$aOchoa, I.$$uUniversidad de Zaragoza
000079010 700__ $$aPérez-García, V.M.
000079010 700__ $$aPešic, M.
000079010 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología
000079010 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000079010 773__ $$g2019 (2019), 3061607 [14 pp]$$pOxidative Medicine and Cellular Longevity$$tOxidative Medicine and Cellular Longevity$$x1942-0900
000079010 8564_ $$s809166$$uhttps://zaguan.unizar.es/record/79010/files/texto_completo.pdf$$yVersión publicada
000079010 8564_ $$s88597$$uhttps://zaguan.unizar.es/record/79010/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000079010 909CO $$ooai:zaguan.unizar.es:79010$$particulos$$pdriver
000079010 951__ $$a2020-07-16-09:13:02
000079010 980__ $$aARTICLE