ArticleCells2021
Omega-3 Fatty Acids DHA and EPA Reduce Bortezomib Resistance in Multiple Myeloma Cells by Promoting Glutathione Degradation.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Genetic evidence reveals phosphatidylcholine as a mediator in the causal relationship between omega-3 and multiple myeloma risk.Scientific reports · 2025Pooled it
- GSH-Related Enzymes GPx4, Chac1, and GSTs and Redox Regulation of Ferroptosis in Cancer.International journal of molecular sciences · 2026Review
- Ferroptosis targeting: a novel therapeutic armamentarium in multiple myeloma.Cancer cell international · 2026Review
- The role of antioxidants in multiple myeloma: diagnostic, prognostic, and therapeutic applications: a narrative review.Therapeutic advances in hematology · 2026Review
- [Progress in metabolomics of multiple myeloma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Review
- PSMA-targeted theranostic nanoplatform achieves spatiotemporally precise therapy and triggers ferroptosis in prostate cancer treatment.Journal of experimental & clinical cancer research : CR · 2025Article
- The instrumental role of lipids in governing the sensitivity of multiple myeloma to ferroptosis.Discover oncology · 2025Review
- Lipid metabolism in multiple myeloma: pathogenesis, therapeutic opportunities, and future directions.Frontiers in oncology · 2025Review
- Ferroptosis: a novel pharmacological mechanism against multiple myeloma.Frontiers in pharmacology · 2025Review
- Class II ferroptosis inducers are a novel therapeutic approach for t(4;14)-positive multiple myeloma.Blood advances · 2024Article
- Research Progress on Ferroptosis in Multiple Myeloma.Current treatment options in oncology · 2024Review
- Different Strategies to Overcome Resistance to Proteasome Inhibitors-A Summary 20 Years after Their Introduction.International journal of molecular sciences · 2024Review
- Glutathione‑degrading enzymes in the complex landscape of tumors (Review).International journal of oncology · 2024Review
- GSH and Ferroptosis: Side-by-Side Partners in the Fight against Tumors.Antioxidants (Basel, Switzerland) · 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
- Ferroptosis-Related Genes in IgA Nephropathy: Screening for Potential Targets of the Mechanism.International journal of genomics · 2024Article
- Multidimensional role of adapalene in regulating cell death in multiple myeloma.Frontiers in pharmacology · 2024Article
- CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers.Frontiers in cell and developmental biology · 2024Review
- Autophagy and oxidative stress modulation mediate Bortezomib resistance in prostate cancer.PloS one · 2024Article
- Polysaccharide dextran-based conjugate for selective co-delivery of two synergistic drugs docetaxel and docosahexaenoic acid to tumor cells.Drug delivery · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple myeloma (MM) is a hematological malignancy that exhibits aberrantly high levels of proteasome activity. While treatment with the proteasome inhibitor bortezomib substantially increases overall survival of MM patients, acquired drug resistance remains the main challenge for MM treatment. Using a combination treatment of docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) and bortezomib, it was demonstrated previously that pretreatment with DHA/EPA significantly increased bortezomib chemosensitivity in MM cells. In the current study, both transcriptome and metabolome analysis were performed to comprehensively evaluate the underlying mechanism. It was demonstrated that pretreating MM cells with DHA/EPA before bortezomib potently decreased the cellular glutathione (GSH) level and altered the expression of the related metabolites and key enzymes in GSH metabolism, whereas simultaneous treatment only showed minor effects on these factors, thereby suggesting the critical role of GSH degradation in overcoming bortezomib resistance in MM cells. Moreover, RNA-seq results revealed that the nuclear factor erythroid 2-related factor 2 (NRF2)-activating transcription factor 3/4 (ATF3/4)-ChaC glutathione specific gamma-glutamylcyclotransferase 1 (CHAC1) signaling pathway may be implicated as the central player in the GSH degradation. Pathways of necroptosis, ferroptosis, p53, NRF2, ATF4, WNT, MAPK, NF-κB, EGFR, and ERK may be connected to the tumor suppressive effect caused by pretreatment of DHA/EPA prior to bortezomib. Collectively, this work implicates GSH degradation as a potential therapeutic target in MM and provides novel mechanistic insights into its significant role in combating bortezomib resistance.
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Registered trials
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.