ArticleAntioxidants (Basel, Switzerland)2022
TLR4 Signaling and Heme Oxygenase-1/Carbon Monoxide Pathway Crosstalk Induces Resiliency of Myeloma Plasma Cells to Bortezomib Treatment.
Article in Antioxidants (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 17 citations in OpenAlex.
- Electrorotation as a tool for the dielectric characterization of tumor plasma cells in multiple myeloma.Scientific reports · 2026Article
- Continuous multi-omics pathway enrichment analysis resolves hidden functional heterogeneity.Briefings in bioinformatics · 2026Article
- Review
- HO-1-driven drug resistance in hematological malignancies: Mechanistic insights and advances in targeted therapy.iScience · 2026Review
- Review
- The role of TLR-4 in chemoresistance of cancer.Discover oncology · 2025Review
- The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Glycine attenuates sepsis-induced white matter injury by modulating gut microbiota.Frontiers in molecular biosciences · 2025Article
- Enhanced Antitumor Activity by the Combination of Dasatinib and Selinexor in Chronic Myeloid Leukemia.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Microglia and glioblastoma heterocellular interplay sustains tumour growth and proliferation as an off-target effect of radiotherapy.Cell proliferation · 2024Article
- Toll-like receptor signaling in multiple myeloma cells promotes the expression of pro-survival genes B-cell lymphoma 2 and MYC and modulates the expression of B-cell maturation antigen.Frontiers in immunology · 2024Article
- MacroH2A1.1 as a crossroad between epigenetics, inflammation and metabolism of mesenchymal stromal cells in myelodysplastic syndromes.Cell death & disease · 2023Article
- The Pleiotropic Effects of Fumarate: From Mitochondrial Respiration to Epigenetic Rewiring and DNA Repair Mechanisms.Metabolites · 2023Review
- Cytoprotective Role of Heme Oxygenase-1 in Cancer Chemoresistance: Focus on Antioxidant, Antiapoptotic, and Pro-Autophagy Properties.Antioxidants (Basel, Switzerland) · 2023Review
- Lactate trafficking inhibition restores sensitivity to proteasome inhibitors and orchestrates immuno-microenvironment in multiple myeloma.Cell proliferation · 2023Article
- Ectopic CH60 mediates HAPLN1-induced cell survival signaling in multiple myeloma.Life science alliance · 2023Article
- Lactate Rewrites the Metabolic Reprogramming of Uveal Melanoma Cells and Induces Quiescence Phenotype.International journal of molecular sciences · 2022Article
- Neuroprotective Role of α-Lipoic Acid in Iron-Overload-Mediated Toxicity and Inflammation in In Vitro and In Vivo Models.Antioxidants (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Relapse in multiple myeloma (MM) decreases therapy efficiency through unclear mechanisms of chemoresistance. Since our group previously demonstrated that heme oxygenase-1 (HO-1) and Toll-like receptor 4 (TLR4) are two signaling pathways protecting MM cells from the proteasome inhibitor bortezomib (BTZ), we here evaluated their cross-regulation by a pharmacological approach. We found that cell toxicity and mitochondrial depolarization by BTZ were increased upon inhibition of HO-1 and TLR4 by using tin protoporphyrin IX (SnPP) and TAK-242, respectively. Furthermore, the combination of TAK-242 and BTZ activated mitophagy and decreased the unfolded protein response (UPR) survival pathway in association with a downregulation in HO-1 expression. Notably, BTZ in combination with SnPP induced effects mirroring the treatment with TAK-242/BTZ, resulting in a blockade of TLR4 upregulation. Interestingly, treatment of cells with either hemin, an HO-1 inducer, or supplementation with carbon monoxide (CO), a by-product of HO-1 enzymatic activity, increased TLR4 expression. In conclusion, we showed that treatment of MM cells with BTZ triggers the TLR4/HO-1/CO axis, serving as a stress-responsive signal that leads to increased cell survival while protecting mitochondria against BTZ and ultimately promoting drug 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.