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Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma In Vitro and In Vivo.

Stojković Burić, Sonja; Podolski-Renić, Ana; Dinić, Jelena; Stanković, Tijana; Jovanović, Mirna; Hadžić, Stefan; Ayuso, Jose M.; Virumbrales-Muñoz, María; Fernández, Luis J.; Ochoa, Ignacio; Pérez-García, Victor M.; Pešić, Milica

(2019)

TY  - JOUR
AU  - Stojković Burić, Sonja
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Jovanović, Mirna
AU  - Hadžić, Stefan
AU  - Ayuso, Jose M.
AU  - Virumbrales-Muñoz, María
AU  - Fernández, Luis J.
AU  - Ochoa, Ignacio
AU  - Pérez-García, Victor M.
AU  - Pešić, Milica
PY  - 2019
UR  - https://www.hindawi.com/journals/omcl/2019/3061607/
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6432727
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3323
AB  - 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.
T2  - Oxidative Medicine and Cellular Longevity
T1  - Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma In Vitro and In Vivo.
VL  - 2019
DO  - 10.1155/2019/3061607
SP  - 3061607
ER  - 
@article{
author = "Stojković Burić, Sonja and Podolski-Renić, Ana and Dinić, Jelena and Stanković, Tijana and Jovanović, Mirna and Hadžić, Stefan and Ayuso, Jose M. and Virumbrales-Muñoz, María and Fernández, Luis J. and Ochoa, Ignacio and Pérez-García, Victor M. and Pešić, Milica",
year = "2019",
abstract = "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.",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma In Vitro and In Vivo.",
volume = "2019",
doi = "10.1155/2019/3061607",
pages = "3061607"
}
Stojković Burić, S., Podolski-Renić, A., Dinić, J., Stanković, T., Jovanović, M., Hadžić, S., Ayuso, J. M., Virumbrales-Muñoz, M., Fernández, L. J., Ochoa, I., Pérez-García, V. M.,& Pešić, M.. (2019). Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma In Vitro and In Vivo.. in Oxidative Medicine and Cellular Longevity, 2019, 3061607.
https://doi.org/10.1155/2019/3061607
Stojković Burić S, Podolski-Renić A, Dinić J, Stanković T, Jovanović M, Hadžić S, Ayuso JM, Virumbrales-Muñoz M, Fernández LJ, Ochoa I, Pérez-García VM, Pešić M. Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma In Vitro and In Vivo.. in Oxidative Medicine and Cellular Longevity. 2019;2019:3061607.
doi:10.1155/2019/3061607 .
Stojković Burić, Sonja, Podolski-Renić, Ana, Dinić, Jelena, Stanković, Tijana, Jovanović, Mirna, Hadžić, Stefan, Ayuso, Jose M., Virumbrales-Muñoz, María, Fernández, Luis J., Ochoa, Ignacio, Pérez-García, Victor M., Pešić, Milica, "Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma In Vitro and In Vivo." in Oxidative Medicine and Cellular Longevity, 2019 (2019):3061607,
https://doi.org/10.1155/2019/3061607 . .
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