ArticleBlood cancer journal2014
The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma.
Article in Blood cancer journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed.
- Oxidative Stress and its Role in Carcinogenesis.Cell biochemistry and biophysics · 2026Review
- CypD Dependent mPTP Opening Is Crucial for Oxidized Mitochondrial DNA Release in Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Marrow leptin-LEPR signaling rewires mitochondrial oxidative metabolism to confer chemoresistance in acute myeloid leukemia.Cell death & disease · 2026Article
- The role of antioxidants in multiple myeloma: diagnostic, prognostic, and therapeutic applications: a narrative review.Therapeutic advances in hematology · 2026Review
- Action of Carnosic Acid Against Melanoma: A Strategy for Selective Radiosensitization with Protection of Non-Tumoral Cells.Current issues in molecular biology · 2025Article
- Gamma-Glutamyl Cysteine Ligase Activity as a Proxy for Human T Cell Function and Drug-Induced Immunosuppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Histone lactylation enhances GCLC expression and thus promotes chemoresistance of colorectal cancer stem cells through inhibiting ferroptosis.Cell death & disease · 2025Article
- Crosstalk Between Autophagy and Oxidative Stress in Hematological Malignancies: Mechanisms, Implications, and Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2025Review
- Therapeutic types and advantages of functionalized nanoparticles in inducing ferroptosis in cancer therapy.Annals of medicine · 2024Review
- Mechanism of RSL3-induced ferroptotic cell death in HT22 cells: crucial role of protein disulfide isomerase.Acta biochimica et biophysica Sinica · 2024Article
- Dual targeting of KDM1A and antioxidants is an effective anticancer strategy.bioRxiv : the preprint server for biology · 2024Article
- Review
- The pleiotropic functions of reactive oxygen species in cancer.Nature cancer · 2024Review
- Inhibition of the glutamate-cysteine ligase catalytic subunit with buthionine sulfoximine enhances the cytotoxic effect of doxorubicin and cyclophosphamide in Burkitt lymphoma cells.Journal of applied genetics · 2024Article
- Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells.Cancers · 2023Article
- The role of the Nrf2/GSH antioxidant system in cisplatin resistance in malignant rhabdoid tumours.Journal of cancer research and clinical oncology · 2023Article
- Increased glucose availability sensitizes pancreatic cancer to chemotherapy.Nature communications · 2023Article
- Article
- Metabolic inhibitor screening identifies dihydrofolate reductase as an inducer of the tumor immune escape mediator CD24.Immunomedicine · 2022Article
8 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
Melphalan (L-PAM) has been an integral part of multiple myeloma (MM) treatment as a conditioning regimen before stem cell transplant (SCT). After initial response, most treated patients experience relapse with an aggressive phenotype. Increased glutathione (GSH) in MM may mediate resistance to L-PAM. We demonstrated that the GSH synthesis inhibitor buthionine sulfoximine (BSO) synergistically enhanced L-PAM activity (inducing 2-4 logs of cell kill) against nine MM cell lines (also in the presence of marrow stroma or cytokines) and in seven primary MM samples (combination indices <1.0). In MM cell lines, BSO significantly (P<0.05) depleted GSH, increased L-PAM-induced single-strand DNA breaks, mitochondrial depolarization, caspase cleavage and apoptosis. L-PAM depleted GSH, but GSH rapidly recovered in a L-PAM-resistant MM cell line unless also treated with BSO. Treatment with N-acetylcysteine antagonized BSO+L-PAM cytotoxicity without increasing GSH. In human MM xenografted into beige-nude-xid mice, BSO significantly depleted MM intracellular GSH and significantly increased apoptosis compared with L-PAM alone. BSO+L-PAM achieved complete responses (CRs) in three MM xenograft models including maintained CRs >100 days, and significantly increased the median event-free survival relative to L-PAM alone. Combining BSO with L-PAM warrants clinical testing in advanced MM.
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