ArticleOncotarget2016
Glutathione-mediated antioxidant response and aerobic metabolism: two crucial factors involved in determining the multi-drug resistance of high-risk neuroblastoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 64 citations in OpenAlex.
- Significance of GSH and HRedox report : communications in free radical research · 2026Review
- Amphiphilic Semisynthetic Triterpenoids Impair Survival Pathways and Suppress Clonogenic Growth in Multidrug-Resistant High-Risk Neuroblastoma.International journal of molecular sciences · 2026Article
- Functional cooperation between the B-cell receptor and NOTCH1 in regulating metabolic reprogramming in chronic lymphocytic leukemia.Leukemia · 2026Article
- Living bacterial reactor potently activates tumor immunogenic ferroptosis via cysteine depletion and photothermal therapy.Materials today. Bio · 2026Article
- Quaternary Phosphonium Salts Outperformed Vemurafenib (PLX) and Etoposide Against BRAFInternational journal of molecular sciences · 2026Article
- Cysteine Metabolism in the Control of Oxidative Stress in Cancer, Focusing on Carbon and Sulfur Metabolism.Advances in experimental medicine and biology · 2026Review
- Design and Synthesis of New Coumarin Hybrids Active Against Drug-Sensitive and Drug-Resistant Neuroblastoma Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Small Extracellular Vesicles Secreted by Cisplatin-Resistant Neuroblastoma Cells Increase Lactate Secretion and Alter Metabolic Pathways in Primary Human Umbilical Vein Endothelial Cells (HUVECs).Journal of personalized medicine · 2025Article
- Antioxidant Food Supplementation in Cancer: Lessons from Clinical Trials and Insights from Preclinical Studies.Antioxidants (Basel, Switzerland) · 2025Review
- Understanding and overcoming multidrug resistance in cancer.Nature reviews. Clinical oncology · 2025Review
- From Early Diagnoses to New Treatments for Liver, Pancreatic, Gastric, and Colorectal Cancers Using Carbon Nanotubes: New Chances Still Underexplored.International journal of molecular sciences · 2025Review
- Triazole-imidazo[1,2-International journal of molecular sciences · 2025Article
- Targeting the p53/xCT/GSH Axis with PRIMA-1International journal of molecular sciences · 2025Article
- TPP-Based Nanovesicles Kill MDR Neuroblastoma Cells and Induce Moderate ROS Increase, While Exerting Low Toxicity Towards Primary Cell Cultures: An In Vitro Study.International journal of molecular sciences · 2025Article
- Tri-Phenyl-Phosphonium-Based Nano Vesicles: A New In Vitro Nanomolar-Active Weapon to Eradicate PLX-Resistant Melanoma Cells.International journal of molecular sciences · 2025Article
- Integration of epigenomic and transcriptomic profiling uncovers EZH2 target genes linked to cysteine metabolism in hepatocellular carcinoma.Cell death & disease · 2024Article
- Strongly ROS-Correlated, Time-Dependent, and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation.International journal of molecular sciences · 2024Article
- The Remarkable and Selective In Vitro Cytotoxicity of Synthesized Bola-Amphiphilic Nanovesicles on Etoposide-Sensitive and -Resistant Neuroblastoma Cells.Nanomaterials (Basel, Switzerland) · 2024Article
- Facile synthesis of an acid-responsive cinnamaldehyde-pendant polycarbonate for enhancing the anticancer efficacy of etoposideRSC advances · 2024Article
- Impaired Mitochondrial Function and Marrow Failure in Patients Carrying a Variant of theInternational journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroblastoma, a paediatric malignant tumor, is initially sensitive to etoposide, a drug to which many patients develop chemoresistance. In order to investigate the molecular mechanisms responsible for etoposide chemoresistance, HTLA-230, a human MYCN-amplified neuroblastoma cell line, was chronically treated with etoposide at a concentration that in vitro mimics the clinically-used dose. The selected cells (HTLA-Chr) acquire multi-drug resistance (MDR), becoming less sensitive than parental cells to high doses of etoposide or doxorubicin. MDR is due to several mechanisms that together contribute to maintaining non-toxic levels of H2O2. In fact, HTLA-Chr cells, while having an efficient aerobic metabolism, are also characterized by an up-regulation of catalase activity and higher levels of reduced glutathione (GSH), a thiol antioxidant compound. The combination of such mechanisms contributes to prevent membrane lipoperoxidation and cell death. Treatment of HTLA-Chr cells with L-Buthionine-sulfoximine, an inhibitor of GSH biosynthesis, markedly reduces their tumorigenic potential that is instead enhanced by the exposure to N-Acetylcysteine, able to promote GSH synthesis.Collectively, these results demonstrate that GSH and GSH-related responses play a crucial role in the acquisition of MDR and suggest that GSH level monitoring is an efficient strategy to early identify the onset of drug resistance and to control the patient's response to therapy.
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Registered trials
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