ArticleOncotarget2016
Inhibition of mitochondrial 2-oxoglutarate dehydrogenase impairs viability of cancer cells in a cell-specific metabolism-dependent manner.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Metabolic Profiling of DistinctInternational journal of molecular sciences · 2025Article
- Modeling Krebs cycle from liver, heart and hepatoma mitochondria, supported Complex I as target for specific inhibition of cancer cell proliferation.Frontiers in oncology · 2025Article
- IDH1 mutation inhibits differentiation of astrocytes and glioma cells with low oxoglutarate dehydrogenase expression by disturbing α-ketoglutarate-related metabolism and epigenetic modification.Life metabolism · 2024Article
- Pathological Interplay between Inflammation and Mitochondria Aggravates Glutamate Toxicity.International journal of molecular sciences · 2024Review
- ALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through mCell reports · 2023Article
- Article
- Effect of Expression of Nuclear-Encoded Cytochrome C Oxidase Subunit 4 Isoforms on Metabolic Profiles of Glioma Cells.Metabolites · 2022Article
- Increasing Inhibition of the Rat Brain 2-Oxoglutarate Dehydrogenase Decreases Glutathione Redox State, Elevating Anxiety and Perturbing Stress Adaptation.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Targeting 2-oxoglutarate dehydrogenase for cancer treatment.American journal of cancer research · 2022Review
- Interplay Between Thiamine and p53/p21 Axes Affects Antiproliferative Action of Cisplatin in Lung Adenocarcinoma Cells by Changing Metabolism of 2-Oxoglutarate/Glutamate.Frontiers in genetics · 2021Article
- Macrophages Switch to an Osteo-Modulatory Profile Upon RANKL Induction in a Medaka (JBMR plus · 2020Article
- Oxidative Stress as an Important Contributor to the Pathogenesis of Psoriasis.International journal of molecular sciences · 2020Review
- Cancer cells with defective oxidative phosphorylation require endoplasmic reticulum-to-mitochondria CaScience signaling · 2020Article
- Activation of Mitochondrial 2-Oxoglutarate Dehydrogenase by Cocarboxylase in Human Lung Adenocarcinoma Cells A549 Is p53/p21-Dependent and Impairs Cellular Redox State, Mimicking the Cisplatin Action.International journal of molecular sciences · 2020Article
- Synthetic analogues of 2-oxo acids discriminate metabolic contribution of the 2-oxoglutarate and 2-oxoadipate dehydrogenases in mammalian cells and tissues.Scientific reports · 2020Article
- Selective Inhibition of 2-Oxoglutarate and 2-Oxoadipate Dehydrogenases by the Phosphonate Analogs of Their 2-Oxo Acid Substrates.Frontiers in chemistry · 2020Article
- Review
- Mitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance.Nature communications · 2019Article
- OGDH promotes the progression of gastric cancer by regulating mitochondrial bioenergetics and Wnt/β-catenin signal pathway.OncoTargets and therapy · 2019Article
- Sestrins at the Interface of ROS Control and Autophagy Regulation in Health and Disease.Oxidative medicine and cellular longevity · 2019Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
2-Oxoglutarate dehydrogenase (OGDH) of the tricarboxylic acid (TCA) cycle is often implied to be inactive in cancer, but this was not experimentally tested. We addressed the question through specific inhibition of OGDH by succinyl phosphonate (SP). SP action on different cancer cells was investigated using indicators of cellular viability and reactive oxygen species (ROS), metabolic profiling and transcriptomics. Relative sensitivity of various cancer cells to SP changed with increasing SP exposure and could differ in the ATP- and NAD(P)H-based assays. Glioblastoma responses to SP revealed metabolic sub-types increasing or decreasing cellular ATP/NAD(P)H ratio under OGDH inhibition. Cancer cell homeostasis was perturbed also when viability indicators were SP-resistant, e.g. in U87 and N2A cells. The transcriptomics database analysis showed that the SP-sensitive cells, such as A549 and T98G, exhibit the lowest expression of OGDH compared to other TCA cycle enzymes, associated with higher expression of affiliated pathways utilizing 2-oxoglutarate. Metabolic profiling confirmed the dependence of cellular SP reactivity on cell-specific expression of the pathways. Thus, oxidative decarboxylation of 2-oxoglutarate is significant for the interdependent homeostasis of NAD(P)H, ATP, ROS and key metabolites in various cancer cells. Assessment of cell-specific responses to OGDH inhibition is of diagnostic value for anticancer strategies.
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