Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide

Frontiñán-Rubio, Javier; Santiago-Mora, Raquel; Nieva-Velasco, Consuelo María; Ferrín, Gustavo; Martínez-González, Alicia; Gómez, M. Victoria; Moreno, Maria Cecilia Rey; Ariza, Julia; Lozano, Eva; Arjona-Gutiérrez, Jacinto; Gil-Agudo, Antonio; Mata, Manuel de la; Pešić, Milica; Peinado, Juan R.; Villalba, José M.; Pérez-Romasanta, Luis Alberto; Pérez-Garcı́a, Vı́ctor M.; Alcaı́n, Francisco J.; Durán-Prado, Mario

doi:10.1016/j.radonc.2018.04.033

Cited by 20 publications

(22 citation statements)

References 43 publications

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“…Although more studies must be performed, this shift to a sustained pro-oxidant state in which GSH is decreased and O 2 .– is augmented leads one to speculate that the sFLG could be inducing in cells a similar effect to that exerted by UV 26 or even radiotherapy. This could lead to DNA damage and probably to the accumulation of DNA mutations 74 . Preliminary evidence already exists for DNA damage generated by different GRMs 75 – 77 and it is worth highlighting the relevance of lateral size, oxidation, dose, etc.…”

Section: Discussionmentioning

confidence: 99%

“…HaCaT cells were seeded in 96 well plates and incubated for 24 h or 7 d with sFLG 5 μg/mL. Total antioxidant capacity was determined in culture media using a commercial kit according to the manufacturer’s instructions (#MAK187, Sigma-Aldrich) as described before 74 . Briefly, supernatants samples were added to wells, then Cu 2+ Working Solution was added.…”

Section: Methodsmentioning

confidence: 99%

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Sublethal exposure of small few-layer graphene promotes metabolic alterations in human skin cells

Frontiñán-Rubio

Gómez

González

et al. 2020

Sci Rep

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Small few-layer graphene (sFLG), a novel small-sized graphene-related material (GRM), can be considered as an intermediate degradation product of graphene. GRMs have a promising present and future in the field of biomedicine. However, safety issues must be carefully addressed to facilitate their implementation. In the work described here, the effect of sub-lethal doses of sFLG on the biology of human HaCaT keratinocytes was examined. A one-week treatment of HaCaTs with sub-lethal doses of sFLG resulted in metabolome remodeling, dampening of the mitochondrial function and a shift in the redox state to pro-oxidant conditions. sFLG raises reactive oxygen species and calcium from 24 h to one week after the treatment and this involves the activation of NADPH oxidase 1. Likewise, sFLG seems to induce a shift from oxidative phosphorylation to glycolysis and promotes the use of glutamine as an alternative source of energy. When sub-toxic sFLG exposure was sustained for 30 days, an increase in cell proliferation and mitochondrial damage were observed. Further research is required to unveil the safety of GRMs and degradation-derived products before their use in the workplace and in practical applications.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Sublethal exposure of small few-layer graphene promotes metabolic alterations in human skin cells

Frontiñán-Rubio

Gómez

González

et al. 2020

Sci Rep

Self Cite

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“…Various diseases associated with CoQ10 deficiency can benefit from CoQ10 supplementation including cardiovascular and neurodegenerative diseases and cancer [21]. Recently, Frontiñán-Rubio et al showed that CoQ10 treatment enhances DNA damage induced by radiation and potentiates TMZ cytotoxicity in human glioblastoma cell lines [22]. In addition, some mathematical works have hypothesized a synergistic effect of antioxidants in combination with chemotherapeutics [23].…”

Section: Introductionmentioning

confidence: 99%

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

Burić

Podolski-Renić

Dinić

et al. 2019

Oxidative Medicine and Cellular Longevity

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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.

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“…PDSS1 encodes the enzyme that elongates the prenyl side-chain of coenzyme Q, or ubiquinone, and may be peripherally associated with the inner mitochondrial membrane. Many studies have investigated the roles of coenzyme Q in suppressing the progression and invasion of glioma cells in vitro and sensitizing GBM cells to TMZ and radiation [ 19 , 20 ]. ID3 encodes a helix-loop-helix (HLH) protein that can form heterodimers with other HLH proteins that are involved in regulating a variety of cellular processes, including cellular growth, differentiation, apoptosis, angiogenesis, and neoplastic transformation [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

A novel hypoxic tumor microenvironment signature for predicting the survival, progression, immune responsiveness and chemoresistance of glioblastoma: a multi-omic study

Wang

Gao

Guo

et al. 2020

Aging

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The hypoxic tumor microenvironment (TME) was reported to promote the aggressive phenotype, progression, recurrence, and chemoresistance of glioblastoma (GBM). We developed and validated a hypoxia gene signature for individualized prognostic prediction in GBM patients. In total, 259 GBM-specific hypoxia-related genes (HRGs) were obtained in hypoxic cultured GBM cells compared with normoxic cells. By applying the k-means algorithm, TCGA GBM patients were divided into two subgroups, and the patients in Cluster 1 exhibited high HRG expression patterns, older age, and poor prognosis, which was validated in the CGGA cohort. Cox regression analyses were performed to generate an HRG-based risk score model consisting of five HRGs, which could reliably discriminate the overall survival (OS) and progression-free survival (PFS) of high- and low-risk patients in both the TCGA training and CGGA validation cohorts. Then, nomograms with the hypoxia signature for OS and PFS prediction were constructed for individualized survival prediction, better treatment decision-making, and follow-up scheduling. Finally, functional enrichment, immune infiltration, immunotherapy response prediction and chemotherapy resistance analyses demonstrated the vital roles of the hypoxic TME in the development, progression, multitherpy resistance of GBM. The hypoxia gene signature could serve as a promising prognostic predictor and potential therapeutic target to combat chemoresistant GBM.

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Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide

Abstract: CoQ acts as sensitizer for cytotoxic therapies, disarming GBM cells, but not normal astrocytes, against further pro-oxidant injuries, being potentially useful in clinical practice for this fatal pathology.

Cited by 20 publications

References 43 publications

Sublethal exposure of small few-layer graphene promotes metabolic alterations in human skin cells

Sublethal exposure of small few-layer graphene promotes metabolic alterations in human skin cells

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

A novel hypoxic tumor microenvironment signature for predicting the survival, progression, immune responsiveness and chemoresistance of glioblastoma: a multi-omic study

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