ArticleRedox biology2020
Higher proteotoxic stress rather than mitochondrial damage is involved in higher neurotoxicity of bortezomib compared to carfilzomib.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Integrative multi-omics profiling reveals an association between lipid metabolism dysregulation and bortezomib-induced cerebral hemorrhage in zebrafish.Fluids and barriers of the CNS · 2026Article
- Using an integrated omics approach to uncover the mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN).Communications medicine · 2026Review
- Gastrodin alleviates bortezomib-induced peripheral neuropathy by inhibiting NF-κB/NLRP3 pathway-mediated microglial inflammation.The Korean journal of pain · 2026Article
- Atorvastatin Protects Against Deleterious Carfilzomib-Induced Transcriptional Changes in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.International journal of molecular sciences · 2026Article
- Global perspectives on lupus nephritis: a review of clinical trials and therapeutic innovations.Frontiers in immunology · 2026Review
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
- Cancer Drug Bortezomib, a Proteasomal Inhibitor, Triggers Cytotoxicity in Microvascular Endothelial Cells via Multi-Organelle Stress.bioRxiv : the preprint server for biology · 2025Article
- Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.Frontiers in pharmacology · 2025Review
- Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis.Blood · 2023Article
- Molecular Cardiotoxic Effects of Proteasome Inhibitors Carfilzomib and Ixazomib and Their Combination with Dexamethasone Involve Mitochondrial Dysregulation.Cardiovascular toxicology · 2023Article
- Animal models of chemotherapy-induced peripheral neuropathy for hematological malignancies: A review.Ibrain · 2023Review
- Current and Emerging Pharmacotherapeutic Interventions for the Treatment of Peripheral Nerve Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Review
- Tracing the NGLY1 footprints: insights from Drosophila.Journal of biochemistry · 2022Review
- Tubulin binding potentially clears up Bortezomib and Carfilzomib differential neurotoxic effect.Scientific reports · 2021Article
- Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy.International journal of molecular sciences · 2021Review
- Article
- Abnormal Mitochondria-Endoplasmic Reticulum Communication Promotes Myocardial Infarction.Frontiers in physiology · 2021Article
- Non-Hematologic Toxicity of Bortezomib in Multiple Myeloma: The Neuromuscular and Cardiovascular Adverse Effects.Cancers · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteasome inhibitors have great success for their therapeutic potential against hematologic malignancies. First generation proteasome inhibitor bortezomib induced peripheral neuropathy is considered as a limiting factor in chemotherapy and its second-generation counterpart carfilzomib is associated with lower rates of neurotoxicity. The mitochondrial toxicity (mitotoxicity) hypothesis arises from studies with animal models of bortezomib induced peripheral neuropathy. However, molecular mechanisms are not fully elucidated and the role of mitotoxicity in bortezomib and carfilzomib induced neurotoxicity has not been investigated comparatively. Herein, we characterized the neurotoxic effects of bortezomib and carfilzomib at the molecular level in human neuronal cells using LC-MS/MS analysis, flow cytometry, RT-qPCR, confocal microscopy and western blotting. We showed that bortezomib and carfilzomib affected the human neuronal proteome differently, and bortezomib caused higher proteotoxic stress via protein oxidation, protein K48-ubiquitination, heat shock protein expression upregulation and reduction of mitochondria membrane potential. Bortezomib and carfilzomib did not affect the gene expression levels related to mitochondrial dynamics (optic atrophy 1; OPA1, mitofusin 1; MFN1, mitofusin 2; MFN2, fission 1; FIS1, dynamin-related protein 1; DRP1) and overall mitophagy rate whereas, PINK1/Parkin mediated mitophagy gene expressions were altered with both drugs. Bortezomib and carfilzomib caused downregulation of the contents of mitochondrial oxidative phosphorylation complexes, voltage-dependent anion channel 1 (VDAC1) and uncoupling protein 2 (UCP2) similarly. Our findings suggest that, both drugs induce mitotoxicity besides proteotoxic stress in human neuronal cells and the higher incidence of neurotoxicity with bortezomib than carfilzomib is not directly related to mitochondrial pathways.
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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.