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Updated: May 8, 2025
Preparation of Mitochondria from Ovarian Cancer Tissues and Control Ovarian Tissues for Quantitative Proteomics Analysis
Published on: November 18, 2019
Singlet Oxygen-Induced Mitochondrial Reset in Cancer: A Novel Approach for Ovarian Cancer Therapy
Jorgelindo da Veiga Moreira1, Laurent Schwartz2, Mario Jolicoeur1
1Research Laboratory in Applied Metabolic Engineering, Department of Chemical Engineering, Polytechnique Montréal, Centre-Ville Station, P.O. Box 6079, Montréal, QC H3C 3A7, Canada.
Abstract:
Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
Insights
Methylene blue-activated singlet oxygen selectively targets ovarian cancer cell metabolism, inhibiting ATP synthesis and proliferation by reversing the Warburg effect. This offers a novel therapeutic strategy for ovarian cancer.
Area of Science:
- Biochemistry
- Oncology
- Photodynamic Therapy
Background:
- Ovarian cancer exhibits altered cellular metabolism, including the Warburg effect.
- Methylene blue (MB) can generate singlet oxygen (SO) upon light activation.
- Targeting cancer metabolism presents a therapeutic opportunity.
Purpose of the Study:
- To investigate singlet oxygen generation via methylene blue as a metabolic intervention for ovarian cancer.
- To assess the impact of SO on mitochondrial function, cellular metabolism, and proliferation in ovarian cancer cells.
- To compare the effects in sensitive (TOV1369) and less sensitive (OV1369-R2) ovarian cancer cell lines and control cells (ARPE-19).
Main Methods:
- Treatment of ovarian cancer cell lines (OV1369-R2, TOV1369) and control cells (ARPE-19) with methylene blue and light activation.
- Assessment of mitochondrial function and ATP synthesis.
- Metabolomic analysis to evaluate central carbon metabolism and Warburg effect markers.
Main Results:
- Methylene blue-activated singlet oxygen significantly inhibited ATP synthesis and proliferation in TOV1369 cells.
- Metabolomic analysis revealed a partial reversal of the Warburg effect, indicating a shift towards oxidative phosphorylation.
- These metabolic and proliferative effects were less pronounced in OV1369-R2 and ARPE-19 cells, correlating with lower MB sensitivity.
Conclusions:
- Methylene blue-generated singlet oxygen selectively modulates mitochondrial energetics in ovarian cancer cells.
- This metabolic reprogramming curtails cancer cell proliferation and holds potential for inducing apoptosis.
- Leveraging cancer's metabolic vulnerabilities, this approach offers a promising therapeutic strategy for ovarian cancer.
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