ArticleCell cycle (Georgetown, Tex.)2016
TrxR1 inhibition overcomes both hypoxia-induced and acquired bortezomib resistance in multiple myeloma through NF-кβ inhibition.
Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Mechanism of palytoxin-induced ferroptosis in HaCaT cells via targeting TrxR1.Cell biology and toxicology · 2026Article
- The role of antioxidants in multiple myeloma: diagnostic, prognostic, and therapeutic applications: a narrative review.Therapeutic advances in hematology · 2026Review
- Compound Taxus exerts marked anti-tumor activity and radiosensitization effect on hepatocellular carcinoma cells.Heliyon · 2024Article
- Regulation of Intestinal Flora and Immune Response by Cyanidin Exhibits Protective Effect against Type-2 Diabetes in Rat Model.Doklady. Biochemistry and biophysics · 2023Article
- Combined thioredoxin reductase and glutaminase inhibition exerts synergistic anti-tumor activity in MYC-high high-grade serous ovarian carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Co-Targeting of BTK and TrxR as a Therapeutic Approach to the Treatment of Lymphoma.Antioxidants (Basel, Switzerland) · 2023Article
- Dual inhibition of thioredoxin reductase and proteasome is required for auranofin-induced paraptosis in breast cancer cells.Cell death & disease · 2023Article
- An mTORC1 to HRI signaling axis promotes cytotoxicity of proteasome inhibitors in multiple myeloma.Cell death & disease · 2022Article
- Article
- Upgrade of an old drug: Auranofin in innovative cancer therapies to overcome drug resistance and to increase drug effectiveness.Medicinal research reviews · 2022Review
- Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-κB Activation: A Review of the Molecular Mechanisms.International journal of molecular sciences · 2021Review
- Ethaselen synergizes with oxaliplatin in tumor growth inhibition by inducing ROS production and inhibiting TrxR1 activity in gastric cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Review
- miR‑875‑5p regulates IR and inflammation via targeting TXNRD1 in gestational diabetes rats.Molecular medicine reports · 2021Article
- Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma.Cellular and molecular life sciences : CMLS · 2021Review
- Shengxian decoction decreases doxorubicin‑induced cardiac apoptosis by regulating the TREM1/NF‑κB signaling pathway.Molecular medicine reports · 2021Article
- Acetylated Thioredoxin Reductase 1 Resists Oxidative Inactivation.Frontiers in chemistry · 2021Article
- Protein Carbonylation and Lipid Peroxidation in Hematological Malignancies.Antioxidants (Basel, Switzerland) · 2020Review
- Oxidative Stress-Inducing Anticancer Therapies: Taking a Closer Look at Their Immunomodulating Effects.Antioxidants (Basel, Switzerland) · 2020Review
- Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) is a B-cell malignancy characterized by an accumulation of abnormal clonal plasma cells in the bone marrow. Introduction of the proteasome-inhibitor bortezomib has improved MM prognosis and survival; however hypoxia-induced or acquired bortezomib resistance remains a clinical problem. This study highlighted the role of thioredoxin reductase 1 (TrxR1) in the hypoxia-induced and acquired bortezomib resistance in MM. Higher TrxR1 gene expression correlated with high-risk disease, adverse overall survival, and poor prognosis in myeloma patients. We demonstrated that hypoxia induced bortezomib resistance in myeloma cells and increased TrxR1 protein levels. Inhibition of TrxR1 using auranofin overcame hypoxia-induced bortezomib resistance and restored the sensitivity of hypoxic-myeloma cells to bortezomib. Hypoxia increased NF-кβ subunit p65 nuclear protein levels and TrxR1 inhibition decreased hypoxia-induced NF-кβ p65 protein levels in the nucleus and reduced the expression of NF-кβ-regulated genes. In addition, higher TrxR1 protein levels were observed in bortezomib-resistant myeloma cells compared to the naïve cells, and its inhibition using either auranofin or TrxR1-specific siRNAs reversed bortezomib resistance. TrxR1 inhibition reduced p65 mRNA and protein expression in bortezomib-resistant myeloma cells, and also decreased the expression of NF-кβ-regulated anti-apoptotic and proliferative genes. Thus, TrxR1 inhibition overcomes both hypoxia-induced and acquired bortezomib resistance by inhibiting the NF-кβ signaling pathway. Our findings demonstrate that elevated TrxR1 levels correlate with the acquisition of bortezomib resistance in MM. We propose considering TrxR1-inhibiting drugs, such as auranofin, either for single agent or combination therapy to circumvent bortezomib-resistance and improve survival outcomes of MM patients.
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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.