ArticleCancers2020
Iron Causes Lipid Oxidation and Inhibits Proteasome Function in Multiple Myeloma Cells: A Proof of Concept for Novel Combination Therapies.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- Dissecting Complex Interactions Between Ferroptosis and the Proteasome.bioRxiv : the preprint server for biology · 2026Article
- Ferroptosis targeting: a novel therapeutic armamentarium in multiple myeloma.Cancer cell international · 2026Review
- Macrophage ferroptosis in hematologic malignancies: emerging mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Programmed cell death in triple-negative breast cancer.Cellular & molecular biology letters · 2025Review
- Peroxiredoxins as novel indicators in multiple myeloma associated with ferroptosis and immune infiltration.Scientific reports · 2025Article
- Novel (1S,3R)-RSL3-Encapsulated Polyunsaturated Fatty Acid Rich Liposomes Sensitise Multiple Myeloma Cells to Ferroptosis-Mediated Cell Death.International journal of molecular sciences · 2025Article
- Ferroptosis: a novel pharmacological mechanism against multiple myeloma.Frontiers in pharmacology · 2025Review
- Research Progress on Ferroptosis in Multiple Myeloma.Current treatment options in oncology · 2024Review
- Targeting ferroptosis for leukemia therapy: exploring novel strategies from its mechanisms and role in leukemia based on nanotechnology.European journal of medical research · 2024Review
- Anaplastic thyroid cancer cells reduce CD71 levels to increase iron overload tolerance.Journal of translational medicine · 2023Article
- α-KG inhibits tumor growth of diffuse large B-cell lymphoma by inducing ROS and TP53-mediated ferroptosis.Cell death discovery · 2023Article
- Ferroptosis in Haematological Malignancies and Associated Therapeutic Nanotechnologies.International journal of molecular sciences · 2023Review
- Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury.Neural regeneration research · 2023Article
- Discovery-Based Proteomics Identify Skeletal Muscle Mitochondrial Alterations as an Early Metabolic Defect in a Mouse Model of β-Thalassemia.International journal of molecular sciences · 2023Article
- Quantitative reactive cysteinome profiling reveals a functional link between ferroptosis and proteasome-mediated degradation.Cell death and differentiation · 2023Article
- Comprehensive analysis of ferroptosis-related genes in immune infiltration and prognosis in multiple myeloma.Frontiers in pharmacology · 2023Article
- Ironing out exercise on immuno-oncological outcomes.Journal for immunotherapy of cancer · 2022Article
- Shikonin induces ferroptosis in multiple myelomaFrontiers in oncology · 2022Article
- Ferroptosis: Redox Imbalance and Hematological Tumorigenesis.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Adaptation to import iron for proliferation makes cancer cells potentially sensitive to iron toxicity. Iron loading impairs multiple myeloma (MM) cell proliferation and increases the efficacy of the proteasome inhibitor bortezomib. Here, we defined the mechanisms of iron toxicity in MM.1S, U266, H929, and OPM-2 MM cell lines, and validated this strategy in preclinical studies using Vk*MYC mice as MM model. High-dose ferric ammonium citrate triggered cell death in all cell lines tested, increasing malondialdehyde levels, the by-product of lipid peroxidation and index of ferroptosis. In addition, iron exposure caused dose-dependent accumulation of polyubiquitinated proteins in highly iron-sensitive MM.1S and H929 cells, suggesting that proteasome workload contributes to iron sensitivity. Accordingly, high iron concentrations inhibited the proteasomal chymotrypsin-like activity of 26S particles and of MM cellular extracts in vitro. In all MM cells, bortezomib-iron combination induced persistent lipid damage, exacerbated bortezomib-induced polyubiquitinated proteins accumulation, and triggered cell death more efficiently than individual treatments. In Vk*MYC mice, addition of iron dextran or ferric carboxymaltose to the bortezomib-melphalan-prednisone (VMP) regimen increased the therapeutic response and prolonged remission without causing evident toxicity. We conclude that iron loading interferes both with redox and protein homeostasis, a property that can be exploited to design novel combination strategies including iron supplementation, to increase the efficacy of current MM therapies.
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Registered trials
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