ArticleBiochimica et biophysica acta2016
Glutamine drives glutathione synthesis and contributes to radiation sensitivity of A549 and H460 lung cancer cell lines.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Immunonutrition for modifying inflammatory markers and improving clinical outcomes following traumatic brain injury: a systematic review and meta-analysis.BMC neurology · 2025Pooled it
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- Cetobacterium somerae ZNN-1 promotes goblet cell differentiation through glutamine-mediated Notch signaling suppression.Journal of advanced research · 2026Article
- Fuelling repair: metabolic regulation of alveolar type 2 cell fate in lung regeneration and disease.Disease models & mechanisms · 2026Review
- Rewiring tumor metabolism: heterogeneity, oncometabolites, and adaptive plasticity.Experimental hematology & oncology · 2026Review
- Extracellular vesicles as modulators of cancer metabolism and microenvironment.Extracellular vesicles and circulating nucleic acids · 2026Review
- TheCancer management and research · 2026Review
- Therapeutic Potential of Glutaminase Inhibition Targeting Metabolic Adaptations in Resistant Melanomas to Targeted Therapy.International journal of molecular sciences · 2025Article
- Metabolomic Prediction of Naphthalene Pneumo-Toxicity in the SnailMetabolites · 2025Article
- Oleanolic Acid Restores Drug Sensitivity in Sorafenib-resistant Hepatocellular Carcinoma: Evidence fromJournal of clinical and translational hepatology · 2025Article
- l-[5-Acta pharmaceutica Sinica. B · 2025Article
- Resistance of HEK-293 and COS-7 cell lines to oxidative stress as a model of metabolic response.Acta biochimica Polonica · 2025Article
- Metabolic-Modulating Effects of Radiation: Undetectable Yet Deadly-A Review on Radiotherapy.Cancers · 2024Review
- CB-839 induces reversible dormancy in lung tumor-cells.European journal of pharmacology · 2024Article
- Glutamine Metabolism and Prostate Cancer.Cancers · 2024Review
- Leukocyte immunoglobulin-like receptor B1 (LILRB1) protects human multiple myeloma cells from ferroptosis by maintaining cholesterol homeostasis.Nature communications · 2024Article
- Enhancing nasopharyngeal carcinoma cell radiosensitivity by suppressing AKT/mTOR via CENP-N knockdown.Journal of translational medicine · 2023Article
- Article
- Dose-effect of polystyrene microplastics on digestive toxicity in chickens (Gallus gallus): Multi-omics reveals critical role of gut-liver axis.Journal of advanced research · 2023Article
15 more citing papers are in PubMed but not listed here.
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8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIncreased glutamine uptake is known to drive cancer cell proliferation, making tumor cells glutamine-dependent. Glutamine provides additional carbon and nitrogen sources for cell growth. The first step in glutamine utilization is its conversion to glutamate by glutaminase (GLS). Glutamate is a precursor for glutathione synthesis, and we investigated the hypothesis that glutamine drives glutathione synthesis and thereby contributes to cellular defense systems.
methodsThe importance of glutamine for glutathione synthesis was studied in H460 and A549 lung cancer cell lines using glutamine-free medium and bis-2-(5-phenyl-acetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) a GLS inhibitor. Metabolic activities were determined by targeted mass spectrometry.
resultsA significant correlation between glutamine consumption and glutathione excretion was demonstrated in H460 and A549 tumor cells. Culturing in the presence of [(13)C5]glutamine demonstrated that by 12h >50% of excreted glutathione was derived from glutamine. Culturing in glutamine-free medium or treatment with BPTES, a GLS-specific inhibitor, reduced cell proliferation and viability and abolished glutathione excretion. Treatment with glutathione-ester prevented BPTES-induced cytotoxicity. Inhibition of GLS markedly radiosensitized the lung tumor cell lines, suggesting an important role of glutamine-derived glutathione in determining radiation sensitivity.
conclusionsWe demonstrate here for the first time that a significant amount of extracellular glutathione is directly derived from glutamine. This finding adds yet another important function to the already known glutamine dependence of tumor cells and probably tumors as well. GENERAL SIGNIFICANCE: Glutamine is essential for synthesis and excretion of glutathione to promote cell growth and viability.
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