ArticlePloS one2017
Complex I inhibition augments dichloroacetate cytotoxicity through enhancing oxidative stress in VM-M3 glioblastoma cells.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- "Villains" Turning Good: Antimycin A and Rotenone, Mitochondrial Respiratory Chain Inhibitors, Protect H9c2 Cardiac Cells Against Insults Triggering the Intrinsic Apoptotic Pathway.International journal of molecular sciences · 2025Article
- Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes.Translational oncology · 2025Review
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Mitochondrial respiratory function is preserved under cysteine starvation via glutathione catabolism in NSCLC.Nature communications · 2024Article
- YY1 Lactylation Aggravates Autoimmune Uveitis by Enhancing Microglial Functions via Inflammatory Genes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The Comparative Experimental Study of Sodium and Magnesium Dichloroacetate Effects on Pediatric PBT24 and SF8628 Cell Glioblastoma Tumors Using a Chicken Embryo Chorioallantoic Membrane Model and on Cells In Vitro.International journal of molecular sciences · 2022Article
- Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1.International journal of molecular sciences · 2021Article
- Suppression of Pyruvate Dehydrogenase Kinase by Dichloroacetate in Cancer and Skeletal Muscle Cells Is Isoform Specific and Partially Independent of HIF-1α.International journal of molecular sciences · 2021Article
- Dichloroacetate and PX-478 exhibit strong synergistic effects in a various number of cancer cell lines.BMC cancer · 2021Article
- Brain Opioid Activity and Oxidative Injury: Different Molecular Scenarios Connecting Celiac Disease and Autistic Spectrum Disorder.Brain sciences · 2020Review
- Competitive glucose metabolism as a target to boost bladder cancer immunotherapy.Nature reviews. Urology · 2020Review
- Metabolic Plasticity of Tumor Cells: How They Do Adapt to Food Deprivation.Advances in experimental medicine and biology · 2020Review
- Review
- Inhibition of glycolysis disrupts cellular antioxidant defense and sensitizes HepG2 cells to doxorubicin treatment.FEBS open bio · 2019Article
- Effects of dichloroacetate as single agent or in combination with GW6471 and metformin in paraganglioma cells.Scientific reports · 2018Article
- The Effectiveness of Dichloroacetate on Human Glioblastoma Xenograft Growth Depends on Na+ and Mg2+ Cations.Dose-response : a publication of International Hormesis SocietyArticle
- Metabolic-targeted Combination Therapy With Dichloroacetate and Metformin Suppresses Glioblastoma Cell Line GrowthIn vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin's reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in VM-M3 GBM cells. Metformin potentiated DCA-induced superoxide production, which was required for enhanced cytotoxicity towards VM-M3 cells observed with the combination. Similarly, rotenone enhanced oxidative stress resultant from DCA treatment and this too was required for the noted augmentation of cytotoxicity. Adenosine monophosphate kinase (AMPK) activation was not observed with the concentration of metformin required to enhance DCA activity. Moreover, addition of an activator of AMPK did not enhance DCA cytotoxicity, whereas an inhibitor of AMPK heightened the cytotoxicity of the combination. Our data indicate that metformin enhancement of DCA cytotoxicity is dependent on complex I inhibition. Particularly, that complex I inhibition cooperates with DCA-induction of glucose oxidation to enhance cytotoxic oxidative stress in VM-M3 GBM cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.