{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:20:55Z","timestamp":1785295255610,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council in Taiwan","award":["111-2320-B-040-007-MY3"],"award-info":[{"award-number":["111-2320-B-040-007-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms232113276","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T06:01:28Z","timestamp":1667282488000},"page":"13276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Disulfiram\/Copper Suppresses Cancer Stem Cell Activity in Differentiated Thyroid Cancer Cells by Inhibiting BMI1 Expression"],"prefix":"10.3390","volume":"23","author":[{"given":"Yung-Lun","family":"Ni","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung City 427213, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Ju","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chung Shan Medical University, Taichung City 402306, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Chia","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chung Shan Medical University, Taichung City 402306, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan-Ting","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung City 427213, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9152-2618","authenticated-orcid":false,"given":"Hsueh-Te","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Anatomy & Cell Biology, National Yang Ming Chiao Tung University, Taipei City 112304, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Bachelor Program in Health Care and Social Work for Indigenous Students, Providence University, Taichung City 433303, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Wei","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chung Shan Medical University, Taichung City 402306, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung City 402306, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.hemonc.2013.05.004","article-title":"Incidence of thyroid cancer in the Kingdom of Saudi Arabia, 2000\u20132010","volume":"6","author":"Hussain","year":"2013","journal-title":"Hematol. 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