ArticleBlood cancer journal2016
Intracellular glutathione determines bortezomib cytotoxicity in multiple myeloma cells.
Article in Blood cancer journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- Spatiotemporal activation of unfolded protein response by combined sonodynamic therapy and proteasome inhibition with bortezomib-conjugated TiN nanoparticles.Bioactive materials · 2026Article
- The role of antioxidants in multiple myeloma: diagnostic, prognostic, and therapeutic applications: a narrative review.Therapeutic advances in hematology · 2026Review
- Exploring Emerging Therapeutic Targets in Osteosarcoma by Revisiting the Immune and Cancer-Intrinsic Hallmarks of Cancer.Cancers · 2025Review
- Enhanced anticancer effect of carfilzomib by codelivery of calcium peroxide nanoparticles targeting endoplasmic reticulum stress.Materials today. Bio · 2025Article
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- Article
- Molecular and cellular mechanisms of chemoresistance in paediatric pre-B cell acute lymphoblastic leukaemia.Cancer metastasis reviews · 2024Review
- Class II ferroptosis inducers are a novel therapeutic approach for t(4;14)-positive multiple myeloma.Blood advances · 2024Article
- Oncogenic Mutant p53 Sensitizes Non-Small Cell Lung Cancer Cells to Proteasome Inhibition via Oxidative Stress-Dependent Induction of Mitochondrial Apoptosis.Cancer research communications · 2024Article
- Different Strategies to Overcome Resistance to Proteasome Inhibitors-A Summary 20 Years after Their Introduction.International journal of molecular sciences · 2024Review
- Article
- Optical Control of Proteasomal Protein Degradation with a Photoswitchable Lipopeptide.Angewandte Chemie (International ed. in English) · 2024Article
- Comprehensive Structure-Activity Relationship Studies of Cepafungin Enabled by Biocatalytic C-H Oxidations.ACS central science · 2023Article
- Dual inhibition of thioredoxin reductase and proteasome is required for auranofin-induced paraptosis in breast cancer cells.Cell death & disease · 2023Article
- Zinc and Zinc Transporters in Dermatology.International journal of molecular sciences · 2022Review
- Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance.Nature communications · 2022Article
- Metabolic Vulnerabilities in Multiple Myeloma.Cancers · 2022Review
- The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance.Frontiers in molecular biosciences · 2022Review
- Contribution of the Tumor Microenvironment to Metabolic Changes Triggering Resistance of Multiple Myeloma to Proteasome Inhibitors.Frontiers in oncology · 2022Review
- Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (myeloma in short) is an incurable cancer of antibody-producing plasma cells that comprise 13% of all hematological malignancies. The proteasome inhibitor bortezomib has improved treatment significantly, but inherent and acquired resistance to the drug remains a problem. We here show that bortezomib-induced cytotoxicity was completely dampened when cells were supplemented with cysteine or its derivative, glutathione (GSH) in ANBL-6 and INA-6 myeloma cell lines. GSH is a major component of the antioxidative defense in eukaryotic cells. Increasing intracellular GSH levels fully abolished bortezomib-induced cytotoxicity and transcriptional changes. Elevated intracellular GSH levels blocked bortezomib-induced nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2)-associated stress responses, including upregulation of the xCT subunit of the Xc- cystine-glutamate antiporter. INA-6 cells conditioned to increasing bortezomib doses displayed reduced bortezomib sensitivity and elevated xCT levels. Inhibiting Xc- activity potentiated bortezomib-induced cytotoxicity in myeloma cell lines and primary cells, and re-established sensitivity to bortezomib in bortezomib-conditioned cells. We propose that intracellular GSH level is the main determinant of bortezomib-induced cytotoxicity in a subset of myeloma cells, and that combined targeting of the proteasome and the Xc- cystine-glutamate antiporter can circumvent bortezomib resistance.
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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.