ArticleRedox biology2015
Combined inhibition of glycolysis, the pentose cycle, and thioredoxin metabolism selectively increases cytotoxicity and oxidative stress in human breast and prostate cancer.
Article in Redox biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 94 citations in OpenAlex.
- Differential Sensitivity to xCT-inhibition by ME1 expression.Molecular cancer therapeutics · 2026Article
- Three Thiol-Reactive Reagents drive Synergistic Lethality in Glioblastoma cells.Research square · 2026Article
- Combination nitazoxanide and auranofin treatment has synergistic anticancer activity in anaplastic thyroid cancer through enhanced activation of oxidative stress that leads to apoptosis.Cancer letters · 2025Article
- Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.Cancer medicine · 2025Review
- Somatic CRISPR tumorigenesis and multiomic analysis reveal a pentose phosphate pathway disruption vulnerability in MPNSTs.Science advances · 2025Article
- Tryptophan-induced transcriptomic changes in the European Seabass are highly dependent on neuroendocrine-immune conditions.Scientific reports · 2025Article
- Metabolic Reprogramming at the Edge of Redox: Connections Between Metabolic Reprogramming and Cancer Redox State.International journal of molecular sciences · 2025Review
- Auranofin inhibition of thioredoxin reductase sensitizes lung neuroendocrine tumor cells (NETs) and small cell lung cancer (SCLC) cells to sorafenib as well as inhibiting SCLC xenograft growth.Cancer biology & therapy · 2024Article
- Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.Molecular cancer · 2024Review
- Targeting ROS in cancer: rationale and strategies.Nature reviews. Drug discovery · 2024Review
- The regulatory roles and clinical significance of glycolysis in tumor.Cancer communications (London, England) · 2024Review
- Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production.Current issues in molecular biology · 2024Review
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Inhibition of thioredoxin-1 enhances the toxicity of glycolysis inhibitor 2-deoxyglucose by downregulating SLC1A5 expression in colorectal cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Auranofin Inhibition of Thioredoxin Reductase Sensitizes Lung Neuroendocrine Tumor Cells (NETs) and Small Cell Lung Cancer (SCLC) Cells to Sorafenib as well as Inhibiting SCLC Xenograft Growth.bioRxiv : the preprint server for biology · 2024Article
- Yeast Rim11 kinase responds to glutathione-induced stress by regulating the transcription of phospholipid biosynthetic genes.Molecular biology of the cell · 2024Article
- Exploring the correlation of glycolysis-related chondroitin polymerizing factor (American journal of cancer research · 2023Article
- Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies.Cancers · 2022Review
- Malic Enzyme 1 Absence in Synovial Sarcoma Shifts Antioxidant System Dependence and Increases Sensitivity to Ferroptosis Induction with ACXT-3102.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Upgrade of an old drug: Auranofin in innovative cancer therapies to overcome drug resistance and to increase drug effectiveness.Medicinal research reviews · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Inhibition of glycolysis using 2-deoxy-d-glucose (2DG, 20mM, 24-48h) combined with inhibition of the pentose cycle using dehydroepiandrosterone (DHEA, 300µM, 24-48h) increased clonogenic cell killing in both human prostate (PC-3 and DU145) and human breast (MDA-MB231) cancer cells via a mechanism involving thiol-mediated oxidative stress. Surprisingly, when 2DG+DHEA treatment was combined with an inhibitor of glutathione (GSH) synthesis (l-buthionine sulfoximine; BSO, 1mM) that depleted GSH>90% of control, no further increase in cell killing was observed during 48h exposures. In contrast, when an inhibitor of thioredoxin reductase (TrxR) activity (Auranofin; Au, 1µM), was combined with 2DG+DHEA or DHEA-alone for 24h, clonogenic cell killing was significantly increased in all three human cancer cell lines. Furthermore, enhanced clonogenic cell killing seen with the combination of DHEA+Au was nearly completely inhibited using the thiol antioxidant, N-acetylcysteine (NAC, 20mM). Redox Western blot analysis of PC-3 cells also supported the conclusion that thioredoxin-1 (Trx-1) oxidation was enhanced by treatment DHEA+Au and inhibited by NAC. Importantly, normal human mammary epithelial cells (HMEC) were not as sensitive to 2DG, DHEA, and Au combinations as their cancer cell counterparts (MDA-MB-231). Overall, these results support the hypothesis that inhibition of glycolysis and pentose cycle activity, combined with inhibition of Trx metabolism, may provide a promising strategy for selectively sensitizing human cancer cells to oxidative stress-induced cell killing.
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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 OpenQuestion graph.