ArticleOncotarget2016
Combining 2-deoxy-D-glucose with fenofibrate leads to tumor cell death mediated by simultaneous induction of energy and ER stress.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Integrative transcriptome-wide analysis of atopic dermatitis for drug repositioning.Communications biology · 2022Pooled it
- Targeting Glycolysis with 2-Deoxy-D-Glucose and Lysosomal Integrity with L-Leucyl-L-Leucine Methyl Ester as Antimelanoma Strategy.Pharmaceutics · 2025Article
- Oxidative phosphorylation and breast cancer progression: insights into PGC-1α's role in mitochondrial function.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Sweet regulation - The emerging immunoregulatory roles of hexoses.Journal of advanced research · 2025Review
- Altered metabolism in cancer: insights into energy pathways and therapeutic targets.Molecular cancer · 2024Review
- The Combined Metabolically Oriented Effect of Fucoidan from the Brown AlgaInternational journal of molecular sciences · 2023Article
- 2-Deoxy-D-Glucose: A Novel Pharmacological Agent for Killing Hypoxic Tumor Cells, Oxygen Dependence-Lowering in Covid-19, and Other Pharmacological Activities.Advances in pharmacological and pharmaceutical sciences · 2023Review
- The Anticancer Ruthenium Compound BOLD-100 Targets Glycolysis and Generates a Metabolic Vulnerability towards Glucose Deprivation.Pharmaceutics · 2022Article
- 2-Deoxy-d-glucose exploits increased glucose metabolism in cancer and viral-infected cells: Relevance to its use in India against SARS-CoV-2.IUBMB life · 2021Review
- 2-Deoxy-d-glucose Promotes Buforin IIb-Induced Cytotoxicity in Prostate Cancer DU145 Cells and Xenograft Tumors.Molecules (Basel, Switzerland) · 2020Article
- Power of two: combination of therapeutic approaches involving glucose transporter (GLUT) inhibitors to combat cancer.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- The contribution of ketone bodies to glycolytic inhibition for the treatment of adult and pediatric glioblastoma.Journal of neuro-oncology · 2020Article
- Metabolic Plasticity in Chemotherapy Resistance.Frontiers in oncology · 2020Review
- 2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents.International journal of molecular sciences · 2019Review
- PFKFB3 inhibition reprograms malignant pleural mesothelioma to nutrient stress-induced macropinocytosis and ER stress as independent binary adaptive responses.Cell death & disease · 2019Article
- Potent and PPARα-independent anti-proliferative action of the hypolipidemic drug fenofibrate in VEGF-dependent angiosarcomas in vitro.Scientific reports · 2019Article
- Tumor metabolism regulating chemosensitivity in ovarian cancer.Genes & cancer · 2018Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Unregulated growth and replication as well as an abnormal microenvironment, leads to elevated levels of stress which is a common trait of cancer. By inducing both energy and endoplasmic reticulum (ER) stress, 2-Deoxy-glucose (2-DG) is particularly well-suited to take advantage of the therapeutic window that heightened stress in tumors provides. Under hypoxia, blocking glycolysis with 2-DG leads to significant lowering of ATP resulting in energy stress and cell death in numerous carcinoma cell types. In contrast, under normoxia, 2-DG at a low-concentration is not toxic in most carcinomas tested, but induces growth inhibition, which is primarily due to ER stress. Here we find a synergistic toxic effect in several tumor cell lines in vitro combining 2-DG with fenofibrate (FF), a drug that has been safely used for over 40 years to lower cholesterol in patients. This combination induces much greater energy stress than either agent alone, as measured by ATP reduction, increased p-AMPK and downregulation of mTOR. Inhibition of mTOR results in blockage of GRP78 a critical component of the unfolded protein response which we speculate leads to greater ER stress as observed by increased p-eIF2α. Moreover, to avoid an insulin response and adsorption by the liver, 2-DG is delivered by slow-release pump yielding significant anti-tumor control when combined with FF. Our results provide promise for developing this combination clinically and others that combine 2-DG with agents that act synergistically to selectively increase energy and ER stress to a level that is toxic to numerous tumor cell types.
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