title: Disulfiram suppresses cancer stem-like properties and STAT3 signaling in triple-negative breast cancer cells.
abstract: In the presence of copper (Cu), disulfiram (DSF) suppresses properties associated with cancer stem cells (CSCs) in breast cancer, but the mechanism of action is poorly understood. In the present study, we observed that DSF/Cu treatment induced apoptosis, mediated by caspase-3 activation in triple-negative breast cancer (TNBC) cells. DSF/Cu treatment also specifically targeted CSC-like cell populations, marked by the inhibition of ALDH1 activity, the suppression of CD44+/CD24-and CD49f+/CD24 + subpopulations, and the subsequent impairment of mammosphere formation. These effects were functionally associated with a significant impact on the STAT3 signaling pathway, characterized by the downregulation of phospho-STAT3, cyclin D1 and survivin. In an MDA-MB-231-derived xenograft model, DSF administration significantly downregulated ALDH1A1, CD44 and phospho-STAT3 levels. These findings show for the first time that DSF suppresses stem-like properties in TNBC by targeting the STAT3 signaling pathway.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Department of Biomedical Research Center, Korea University Guro Hospital, Korea University, Seoul 152-703, Republic of Korea.
authors.forename: Yoon-Jae
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea.
authors.forename: Nahyun
authors.initials: N
authors.lastname: Lee
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea.
authors.forename: Eunhye
authors.initials: E
authors.lastname: Oh
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea.
authors.forename: Daeil
authors.initials: D
authors.lastname: Sung
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea.
authors.forename: Tae-Min
authors.initials: TM
authors.lastname: Cho
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea. Electronic address: cancer@korea.ac.kr.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Seo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004221:Disulfiram / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D004221:Disulfiram
keywords: ALDH1A1; Cancer stem cells; Disulfiram; Mammosphere; STAT3; Triple-negative breast cancer