ArticleCancer medicine2023
Hypoxia-induced oxidative stress promotes therapy resistance via upregulation of heme oxygenase-1 in multiple myeloma.
Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- STAT3 inhibition eradicates multiple myeloma stem-like cells and induces immunogenic cell death.Blood science (Baltimore, Md.) · 2026Article
- Mitochondrial OXPHOS restricts SARS-CoV-2 replication.Science advances · 2026Article
- Coumarin- and Dipicolylamine-Terpenoid Hybrids as Selective Carbonic Anhydrases IX and XII Inhibitors: Mechanistic Insights and Selective Anti-Cancer Potential.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Oxidative Stress in Multiple Myeloma: Pathogenic Mechanisms, Biomarkers, and Redox-Targeted Therapeutic Strategies.International journal of molecular sciences · 2026Review
- HO-1-driven drug resistance in hematological malignancies: Mechanistic insights and advances in targeted therapy.iScience · 2026Review
- Combination nitazoxanide and auranofin treatment has synergistic anticancer activity in anaplastic thyroid cancer through enhanced activation of oxidative stress that leads to apoptosis.Cancer letters · 2025Article
- Inhibition of CDC27 O-GlcNAcylation coordinates the antitumor efficacy in multiple myeloma through the autophagy-lysosome pathway.Acta pharmacologica Sinica · 2025Article
- MAFB: a key regulator of myeloid commitment involved in hematological diseases.Cell death discovery · 2025Review
- Prognostic Value of PSMB5 and Correlations with LC3II and Reactive Oxygen Species Levels in the Bone Marrow Mononuclear Cells of Bortezomib-Resistant Multiple Myeloma Patients.Current issues in molecular biology · 2025Article
- Revisiting reactive oxygen species production in hypoxia.Pflugers Archiv : European journal of physiology · 2024Review
- Comprehensive analysis of microRNAs modulated by histone deacetylase inhibitors identifies microRNA-7-5p with anti-myeloma effect.International journal of hematology · 2024Article
- Novel Acetamide-Based HO-1 Inhibitor Counteracts Glioblastoma Progression by Interfering with the Hypoxic-Angiogenic Pathway.International journal of molecular sciences · 2024Article
- Pioglitazone, a peroxisome proliferator‑activated receptor γ agonist, induces cell death and inhibits the proliferation of hypoxic HepG2 cells by promoting excessive production of reactive oxygen species.Oncology letters · 2024Article
- Article
- Acute accumulation of PIM2 and NRF2 and recovery of β5 subunit activity mitigate multiple myeloma cell susceptibility to proteasome inhibitors.International journal of hematology · 2024Article
- Hypoxia-induced oxidative stress promotes therapy resistance via upregulation of heme oxygenase-1 in multiple myeloma.Cancer medicine · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultiple myeloma (MM) is a hematopoietic malignancy for which proteasome inhibitors have become available in recent years. However, many patients develop resistance to these drugs during treatment. Therefore, it is important to elucidate the mechanisms underlying resistance acquisition by proteasome inhibitors. Side population (SP) cells, which have a high drug efflux capacity and hypoxic responses in the microenvironment have both provided important insights into drug resistance in MM; however, little is known about the characteristics of SP cells in hypoxic microenvironments.
methodsWe performed cDNA microarray analysis for SP and non-SP obtained from RPMI-8226 and KMS-11 cell lines cultured for 48 h in normoxic and hypoxic conditions (1% O
resultsOur comprehensive gene expression analysis identified HMOX1, BACH2, and DUX4 as protein-coding genes that are specifically highly expressed in SP cells under hypoxic conditions. We have shown that HMOX1/heme oxygenase-1 (HMOX1/HO-1) is induced by hypoxia-inducible reactive oxygen species (ROS) and reduces ROS levels. Furthermore, we found that HMOX1 contributes to hypoxia-induced resistance to proteasome inhibitors in vitro and in vivo. Excessive ROS levels synergistically enhance bortezomib sensitivity. In clinical datasets, HMOX1 had a strong and significantly positive correlation with MAFB but not MAF. Interestingly, hypoxic stimulation increased MAFB/MafB expression in myeloma cells; in addition, the knockdown of MAFB under hypoxic conditions suppressed HMOX1 expression.
conclusionThese results suggest that the hypoxia-ROS-HMOX1 axis and hypoxia-induced MafB may be important mechanisms of proteasome inhibitor resistance in hypoxic microenvironments.
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