ArticleOncotarget2016
Metabolic reprogramming of glioblastoma cells by L-asparaginase sensitizes for apoptosis in vitro and in vivo.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- Fusion Protein Technology to Enhance Pharmacological Properties of L-Asparaginases.Biomolecules · 2026Review
- Production of L-asparaginase from Candida utilis by solid-state fermentation: a comprehensive assessment of its antiproliferative potential on glioblastoma cells.World journal of microbiology & biotechnology · 2025Article
- Characterization and bioactivities of glutaminase-free L-asparaginase from Salinicola acorporae S4-41.Microbial cell factories · 2025Article
- Marine-derived L-asparaginase: unlocking marine power in anti-tumor therapeutics.Frontiers in immunology · 2025Review
- Exploring the potential of asparagine restriction in solid cancer treatment: recent discoveries, therapeutic implications, and challenges.Medical oncology (Northwood, London, England) · 2024Review
- Nonclinical Evaluation of Single-MutantInternational journal of molecular sciences · 2024Article
- Metabolomic Profiles of Human Glioma Inform Patient Survival.Antioxidants & redox signaling · 2023Review
- Rewired Metabolism of Amino Acids and Its Roles in Glioma Pathology.Metabolites · 2022Review
- Biochemical and Biological Evaluation of an L-Asparaginase from Isolated Escherichia coli MF-107 as an Anti-Tumor Enzyme on MCF7 Cell LineIranian biomedical journal · 2022Article
- Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics.Frontiers in immunology · 2022Review
- Methodological Approaches for Assessing Metabolomic Changes in Glioblastomas.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Article
- Overcoming TRAIL Resistance for Glioblastoma Treatment.Biomolecules · 2021Review
- The evolution of the cancer stem cell state in glioblastoma: emerging insights into the next generation of functional interactions.Neuro-oncology · 2021Review
- Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types.Frontiers in pharmacology · 2021Review
- Recent Strategies and Applications for l-Asparaginase Confinement.Molecules (Basel, Switzerland) · 2020Review
- Epigenetic Targeting of Mcl-1 Is Synthetically Lethal with Bcl-xL/Bcl-2 Inhibition in Model Systems of Glioblastoma.Cancers · 2020Article
- Aspirin Induced Glioma Apoptosis through Noxa Upregulation.International journal of molecular sciences · 2020Article
- Dual metabolic reprogramming by ONC201/TIC10 and 2-Deoxyglucose induces energy depletion and synergistic anti-cancer activity in glioblastoma.British journal of cancer · 2020Article
- L-asparaginase and 6-diazo-5-oxo-L-norleucine synergistically inhibit the growth of glioblastoma cells.Journal of neuro-oncology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Cancer cells display a variety of global metabolic changes, which aside from the glycolytic pathway largely involve amino acid metabolism. To ensure aggressive growth, tumor cells highly depend on amino acids, most notably due to their pivotal need of protein synthesis. In this study, we assessed the overall hypothesis that depletion of asparagine by E. coli-derived L-asparaginase might be a novel means for the therapy of one of the most recalcitrant neoplasms and for which no efficient treatment currently exists - glioblastoma (WHO grade IV). Our results suggest that certain glioma cell cultures are particularly susceptible to inhibition of proliferation by L-asparaginase, while others display a more resistant phenotype. In sensitive cells, L-asparaginase induces apoptosis with dissipation of mitochondrial membrane potential and activation of effector caspases. L-asparaginase-mediated apoptosis was accompanied by modulation of pro- and anti-apoptotic Bcl-2 family members, including Noxa, Mcl-1 and the deubiquitinase Usp9X. Given the impact of L-asparaginase on these molecules, we found that L-asparaginase potently overcomes resistance to both intrinsic apoptosis induced by the Bcl-2/Bcl-xL inhibitor, ABT263, and extrinsic apoptosis mediated by TRAIL even in glioma cells that are resistant towards L-asparaginase single treatment. RNA interference studies showed that Usp9X, Mcl-1, Noxa and Bax/Bak are involved in ABT263/L-asparaginase-mediated cell death. In vivo, combined treatment with ABT263 and L-asparaginase led to an enhanced reduction of tumor growth when compared to each reagent alone without induction of toxicity. These observations suggest that L-asparaginase might be useful for the treatment of malignant glial neoplasms.
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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.