Singlet Oxygen-Induced Mitochondrial Reset in Cancer: A Novel Approach for Ovarian Cancer Therapy

<b>Background/Objectives</b>: This study explores the generation of singlet oxygen (SO) through methylene blue (MB) activation as a metabolic intervention for ovarian cancer. We aimed to examine the role of SO in modulating mitochondrial function, cellular metabolism, and proliferation i...

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Main Authors: Jorgelindo da Veiga Moreira, Laurent Schwartz, Mario Jolicoeur
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/14/12/648
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author Jorgelindo da Veiga Moreira
Laurent Schwartz
Mario Jolicoeur
author_facet Jorgelindo da Veiga Moreira
Laurent Schwartz
Mario Jolicoeur
author_sort Jorgelindo da Veiga Moreira
collection DOAJ
description <b>Background/Objectives</b>: This study explores the generation of singlet oxygen (SO) through methylene blue (MB) activation as a metabolic intervention for ovarian cancer. We aimed to examine the role of SO in modulating mitochondrial function, cellular metabolism, and proliferation in ovarian cancer cell lines compared to control cells. <b>Methods</b>: The study utilized two ovarian cancer cell lines, OV1369-R2 and TOV1369, along with ARPE-19 control cells. Following MB treatment and light activation, mitochondrial function and ATP synthesis were assessed. Metabolomic analyses were performed to evaluate changes in central carbon metabolism, particularly focusing on markers of the Warburg effect. <b>Results</b>: TOV1369 cells exhibited a pronounced sensitivity to MB treatment, resulting in significant inhibition of ATP synthesis and reduced proliferation. Metabolomic analysis indicated that MB-induced SO production partially reversed the Warburg effect, suggesting a shift from glycolysis to oxidative phosphorylation. These effects were less pronounced in OV1369-R2 and ARPE-19 cells, correlating with their lower MB sensitivity. <b>Conclusions</b>: MB-generated SO selectively modulates mitochondrial energetics in ovarian cancer cells, driving a metabolic reorganization that curtails their proliferative capacity. This approach, leveraging the bacterial-like features of cancer metabolism, offers a promising therapeutic avenue to induce apoptosis and enhance treatment outcomes in ovarian cancer.
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spelling doaj-art-e9935231eafd444db81140657d80f7372025-08-20T02:00:29ZengMDPI AGMetabolites2218-19892024-11-01141264810.3390/metabo14120648Singlet Oxygen-Induced Mitochondrial Reset in Cancer: A Novel Approach for Ovarian Cancer TherapyJorgelindo da Veiga Moreira0Laurent Schwartz1Mario Jolicoeur2Research Laboratory in Applied Metabolic Engineering, Department of Chemical Engineering, Polytechnique Montréal, Centre-Ville Station, P.O. Box 6079, Montréal, QC H3C 3A7, CanadaAssistance Publique des Hôpitaux de Paris, Avenue Victoria, 75003 Paris, FranceResearch Laboratory in Applied Metabolic Engineering, Department of Chemical Engineering, Polytechnique Montréal, Centre-Ville Station, P.O. Box 6079, Montréal, QC H3C 3A7, Canada<b>Background/Objectives</b>: This study explores the generation of singlet oxygen (SO) through methylene blue (MB) activation as a metabolic intervention for ovarian cancer. We aimed to examine the role of SO in modulating mitochondrial function, cellular metabolism, and proliferation in ovarian cancer cell lines compared to control cells. <b>Methods</b>: The study utilized two ovarian cancer cell lines, OV1369-R2 and TOV1369, along with ARPE-19 control cells. Following MB treatment and light activation, mitochondrial function and ATP synthesis were assessed. Metabolomic analyses were performed to evaluate changes in central carbon metabolism, particularly focusing on markers of the Warburg effect. <b>Results</b>: TOV1369 cells exhibited a pronounced sensitivity to MB treatment, resulting in significant inhibition of ATP synthesis and reduced proliferation. Metabolomic analysis indicated that MB-induced SO production partially reversed the Warburg effect, suggesting a shift from glycolysis to oxidative phosphorylation. These effects were less pronounced in OV1369-R2 and ARPE-19 cells, correlating with their lower MB sensitivity. <b>Conclusions</b>: MB-generated SO selectively modulates mitochondrial energetics in ovarian cancer cells, driving a metabolic reorganization that curtails their proliferative capacity. This approach, leveraging the bacterial-like features of cancer metabolism, offers a promising therapeutic avenue to induce apoptosis and enhance treatment outcomes in ovarian cancer.https://www.mdpi.com/2218-1989/14/12/648singlet oxygenovarian cancermethylene bluemitochondrial involutionmetabolic bistability
spellingShingle Jorgelindo da Veiga Moreira
Laurent Schwartz
Mario Jolicoeur
Singlet Oxygen-Induced Mitochondrial Reset in Cancer: A Novel Approach for Ovarian Cancer Therapy
Metabolites
singlet oxygen
ovarian cancer
methylene blue
mitochondrial involution
metabolic bistability
title Singlet Oxygen-Induced Mitochondrial Reset in Cancer: A Novel Approach for Ovarian Cancer Therapy
title_full Singlet Oxygen-Induced Mitochondrial Reset in Cancer: A Novel Approach for Ovarian Cancer Therapy
title_fullStr Singlet Oxygen-Induced Mitochondrial Reset in Cancer: A Novel Approach for Ovarian Cancer Therapy
title_full_unstemmed Singlet Oxygen-Induced Mitochondrial Reset in Cancer: A Novel Approach for Ovarian Cancer Therapy
title_short Singlet Oxygen-Induced Mitochondrial Reset in Cancer: A Novel Approach for Ovarian Cancer Therapy
title_sort singlet oxygen induced mitochondrial reset in cancer a novel approach for ovarian cancer therapy
topic singlet oxygen
ovarian cancer
methylene blue
mitochondrial involution
metabolic bistability
url https://www.mdpi.com/2218-1989/14/12/648
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AT laurentschwartz singletoxygeninducedmitochondrialresetincanceranovelapproachforovariancancertherapy
AT mariojolicoeur singletoxygeninducedmitochondrialresetincanceranovelapproachforovariancancertherapy