ArticleInternational journal of molecular sciences2022
Disulfiram/Copper Suppresses Cancer Stem Cell Activity in Differentiated Thyroid Cancer Cells by Inhibiting BMI1 Expression.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Current Studies on the Hypoxic Tumor Microenvironment in Thyroid Cancer: From Molecular Mechanisms to Clinical Therapeutic Perspectives.Biomedicines · 2026Review
- Copper Transporter 1‑Mediated Deregulation of Copper Homeostasis Impacts MYC and Oxidative Phosphorylation Pathways and Increases the Sensitivity of Tumor Cells to Complex I Inhibitors.ACS pharmacology & translational science · 2026Article
- Ambivalent Copper: Mechanistically Distinct Immune Effects Driving Innovation in Cancer Nanomedicine.Pharmaceutics · 2026Review
- The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer.Signal transduction and targeted therapy · 2025Review
- Identification of oxidative stress-related subgroups and signature genes for the prediction of prognosis and immune microenvironment in thyroid cancer.Molecular genetics and genomics : MGG · 2025Article
- A Cuproptosis-Related gene Signature as a Prognostic Biomarker in Thyroid Cancer Based on Transcriptomics.Biochemical genetics · 2025Article
- Effects of Trace Elements on Endocrine Function and Pathogenesis of Thyroid Diseases-A Literature Review.Nutrients · 2025Review
- Atomoxetine suppresses radioresistance in glioblastoma via circATIC/miR-520d-5p/Notch2-Hey1 axis.Cell communication and signaling : CCS · 2024Article
- Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Disulfiram/Copper Activates ER Stress to Promote Immunogenic Cell Death of Oral Squamous Cell Carcinoma.Cell biochemistry and biophysics · 2024Article
- Special Issue: "Drug Repurposing for Cancer Therapies".International journal of molecular sciences · 2024Article
- Targeting the initiator to activate both ferroptosis and cuproptosis for breast cancer treatment: progress and possibility for clinical application.Frontiers in pharmacology · 2024Review
- Polymer/copper nanocomplex-induced lysosomal cell death promotes tumor lymphocyte infiltration and synergizes anti-PD-L1 immunotherapy for triple-negative breast cancer.Biomaterials science · 2023Article
- Identification of a Novel Cuproptosis-Related Gene Signature and Integrative Analyses in Thyroid Cancer.Journal of clinical medicine · 2023Article
- Potential of Copper and Copper Compounds for Anticancer Applications.Pharmaceuticals (Basel, Switzerland) · 2023Review
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
Differentiated thyroid carcinomas (DTCs), which have papillary and follicular types, are common endocrine malignancies worldwide. Cancer stem cells (CSCs) are a particular type of cancer cells within bulk tumors involved in cancer initiation, drug resistance, and metastasis. Cells with high intracellular aldehyde hydrogenase (ALDH) activity are a population of CSCs in DTCs. Disulfiram (DSF), an ALDH inhibitor used for the treatment of alcoholism, reportedly targets CSCs in various cancers when combined with copper. This study reported for the first time that DSF/copper can inhibit the proliferation of papillary and follicular DTC lines. DSF/copper suppressed thyrosphere formation, indicating the inhibition of CSC activity. Molecular mechanisms of DSF/copper involved downregulating the expression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and cell cycle-related proteins, including cyclin B2, cyclin-dependent kinase (CDK) 2, and CDK4, in a dose-dependent manner. BMI1 overexpression diminished the inhibitory effect of DSF/copper in the thyrosphere formation of DTC cells. BMI1 knockdown by RNA interference in DTC cells also suppressed the self-renewal capability. DSF/copper could inhibit the nuclear localization and transcriptional activity of c-Myc and the binding of E2F1 to the BMI1 promoter. Overexpression of c-Myc or E2F1 further abolished the inhibitory effect of DSF/copper on BMI1 expression, suggesting that the suppression of c-Myc and E2F1 by DSF/copper was involved in the downregulation of BMI1 expression. In conclusion, DSF/copper targets CSCs in DTCs by inhibiting c-Myc- or E2F1-mediated BMI1 expression. Therefore, DSF is a potential therapeutic agent for future therapy in DTCs.
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