ArticleOncogene2015
Impairment of antioxidant defense via glutathione depletion sensitizes acute lymphoblastic leukemia cells for Smac mimetic-induced cell death.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Macrophage NLRP3 activation and IL-1β release drive osimertinib-induced antitumor immunity.Journal for immunotherapy of cancer · 2025Article
- XPO1 inhibition displays anti-leukemia efficacy against DNMT3A-mutant acute myeloid leukemia via downregulating glutathione pathway.Annals of hematology · 2024Article
- GAS1 Promotes Ferroptosis of Liver Cells in Acetaminophen-Induced Acute Liver Failure.International journal of medical sciences · 2023Article
- Acute lymphoblastic leukemia necessitates GSH-dependent ferroptosis defenses to overcome FSP1-epigenetic silencing.Redox biology · 2022Article
- Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?Antioxidants (Basel, Switzerland) · 2022Review
- The Role of Redox Status Changes in Dexamethasone-Induced Apoptosis in Jurkat Tumor Cells.Bulletin of experimental biology and medicine · 2022Article
- Ferroptosis: A Novel Therapeutic Direction of Spinal Cord Injury.Computational and mathematical methods in medicine · 2022Review
- Biological Actions and Molecular Mechanisms ofMolecules (Basel, Switzerland) · 2021Article
- Redox Control in Acute Lymphoblastic Leukemia: From Physiology to Pathology and Therapeutic Opportunities.Cells · 2021Review
- Se improves GPX4 expression and SOD activity to alleviate heat-stress-induced ferroptosis-like death in goat mammary epithelial cells.Animal cells and systems · 2021Article
- Oxidative resistance of leukemic stem cells and oxidative damage to hematopoietic stem cells under pro-oxidative therapy.Cell death & disease · 2020Review
- Xanomeline Protects Cortical Cells From Oxygen-Glucose Deprivation via Inhibiting Oxidative Stress and Apoptosis.Frontiers in physiology · 2020Article
- Reactive oxygen species in haematopoiesis: leukaemic cells take a walk on the wild side.Journal of experimental & clinical cancer research : CR · 2018Review
- New insights into redox homeostasis as a therapeutic target in B-cell malignancies.Current opinion in hematology · 2017Review
- Article
- RSL3 and Erastin differentially regulate redox signaling to promote Smac mimetic-induced cell death.Oncotarget · 2016Article
- Emerging roles for lipids in non-apoptotic cell death.Cell death and differentiation · 2016Review
- Mechanisms of ferroptosis.Cellular and molecular life sciences : CMLS · 2016Review
- Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma.Nanomaterials (Basel, Switzerland) · 2015Article
- Redox regulation of Smac mimetic-induced cell death.Molecular & cellular oncologyArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evasion of apoptosis in pediatric acute lymphoblastic leukemia (ALL) is linked to aberrant expression of inhibitor of apoptosis (IAP) proteins and dysregulated redox homeostasis, rendering leukemic cells vulnerable to redox-targeting therapies. Here we discover that inhibition of antioxidant defenses via glutathione (GSH) depletion by buthionine sulfoximine (BSO) primes ALL cells for apoptosis induced by the Smac mimetic BV6 that antagonizes IAP proteins. Similarly, BSO cooperates with BV6 to induce cell death in patient-derived primary leukemic samples, underscoring the clinical relevance. In contrast, BSO does not sensitize non-malignant lymphohematopoietic cells from healthy donors toward BV6, pointing to some tumor selectivity. Mechanistically, both agents cooperate to stimulate reactive oxygen species (ROS) production, which is required for BSO/BV6-induced cell death, as ROS inhibitors (that is, N-acetylcysteine, MnTBAP, Trolox) significantly rescue cell death. Further, BSO and BV6 cooperate to trigger lipid peroxidation, which is necessary for cell death, as genetic or pharmacological blockage of lipid peroxidation by GSH peroxidase 4 (GPX4) overexpression or α-tocopherol significantly inhibits BSO/BV6-mediated cell death. Consistently, GPX4 knockdown or GPX4 inhibitor RSL3 enhances lipid peroxidation and cell death by BSO/BV6 cotreatment. The discovery of redox regulation of Smac mimetic-induced cell death has important implications for developing rational Smac mimetic-based combination therapies.
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