ArticleInternational journal of molecular sciences2021
Suppression of Pyruvate Dehydrogenase Kinase by Dichloroacetate in Cancer and Skeletal Muscle Cells Is Isoform Specific and Partially Independent of HIF-1α.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): diagnosis and management.Journal of translational medicine · 2025Review
- Targeting Metabolic Vulnerabilities Reveals Hexokinase 2 as a Key Mediator of Resistance to Osimertinib in Non-Small Cell Lung Cancer Models.ACS pharmacology & translational science · 2025Article
- Exploring Cirrhosis: Insights into Advances in Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Dichloroacetate and Salinomycin as Therapeutic Agents in Cancer.Medical sciences (Basel, Switzerland) · 2025Review
- Mechanisms for Regulatory Effects of Exercise on Metabolic Diseases from the Lactate-Lactylation Perspective.International journal of molecular sciences · 2025Review
- Recent Advances on the Role of B Vitamins in Cancer Prevention and Progression.International journal of molecular sciences · 2025Review
- Endurance training and pyruvate dehydrogenase kinase 4 (PDK4) inhibition combination is superior to each one alone in attenuating hyperketonemia/ketoacidosis in diabetic rats.Iranian journal of basic medical sciences · 2025Article
- Tumor energy metabolism: implications for therapeutic targets.Molecular biomedicine · 2024Review
- ING5 inhibits aerobic glycolysis of lung cancer cells by promoting TIE1-mediated phosphorylation of pyruvate dehydrogenase kinase 1 at Y163.Frontiers of medicine · 2024Article
- Inhibition of the ubiquitin-proteasome system reduces the abundance of pyruvate dehydrogenase kinase 1 in cultured myotubes.Journal of muscle research and cell motility · 2024Article
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Dichloroacetic acid and rapamycin synergistically inhibit tumor progression.Journal of Zhejiang University. Science. B · 2023Article
- The expression pattern of pyruvate dehydrogenase kinases predicts prognosis and correlates with immune exhaustion in clear cell renal cell carcinoma.Scientific reports · 2023Article
- AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer.Journal of Zhejiang University. Science. B · 2023Article
- Neuronal Agrin Promotes Proliferation of Primary Human Myoblasts in an Age-Dependent Manner.International journal of molecular sciences · 2022Article
- Pyruvate Dehydrogenase Kinase Inhibition by Dichloroacetate in Melanoma Cells Unveils Metabolic Vulnerabilities.International journal of molecular sciences · 2022Article
- Heterogeneous Expression and Subcellular Localization of Pyruvate Dehydrogenase Complex in Prostate Cancer.Frontiers in oncology · 2022Article
- hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway.Frontiers in oncology · 2021Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical UniversityArticle
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Inhibition of pyruvate dehydrogenase kinase (PDK) emerged as a potential strategy for treatment of cancer and metabolic disorders. Dichloroacetate (DCA), a prototypical PDK inhibitor, reduces the abundance of some PDK isoenzymes. However, the underlying mechanisms are not fully characterized and may differ across cell types. We determined that DCA reduced the abundance of PDK1 in breast (MDA-MB-231) and prostate (PC-3) cancer cells, while it suppressed both PDK1 and PDK2 in skeletal muscle cells (L6 myotubes). The DCA-induced PDK1 suppression was partially dependent on hypoxia-inducible factor-1α (HIF-1α), a transcriptional regulator of PDK1, in cancer cells but not in L6 myotubes. However, the DCA-induced alterations in the mRNA and the protein levels of PDK1 and/or PDK2 did not always occur in parallel, implicating a role for post-transcriptional mechanisms. DCA did not inhibit the mTOR signaling, while inhibitors of the proteasome or gene silencing of mitochondrial proteases CLPP and AFG3L2 did not prevent the DCA-induced reduction of the PDK1 protein levels. Collectively, our results suggest that DCA reduces the abundance of PDK in an isoform-dependent manner via transcriptional and post-transcriptional mechanisms. Differential response of PDK isoenzymes to DCA might be important for its pharmacological effects in different types of cells.
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