title: Disulfiram inhibits TGF-β-induced epithelial-mesenchymal transition and stem-like features in breast cancer via ERK/NF-κB/Snail pathway.
abstract: Disulfiram (DSF), an anti-alcoholism drug, has been reported as an inhibitor of NF-κB. NF-κB is involved in epithelial-mesenchymal transition (EMT) and self-renewal of breast cancer stem cells (CSCs). In this study, we treated MCF-7 and MDA-MB-231 breast cancer cells with TGF-β to induce EMT and cancer stem-like features and studied whether DSF can reverse this process. We found that DSF inhibited TGF-β induced EMT in breast cancer cells in a dose-dependent manner. Also, DSF inhibited EMT-associated stem-like features, migration and invasion of tumor cells as well as tumor growth in xenograft model. The activation of NF-κB was linked with EMT and stem-like cells. We conclude that DSF can suppress NF-κB activity and downregulate ERK/NF-κB/Snail pathway, leading to reverse EMT and stem-like features. Our data suggest that DSF inhibits EMT and stem-like properties in breast cancer cells associated with inhibition of the ERK/NF-κB/Snail pathway.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Han
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Chang
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qiuhui
authors.initials: Q
authors.lastname: Li
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000427:Alcohol Deterrents / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004221:Disulfiram / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000427:Alcohol Deterrents; D016328:NF-kappa B; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D004221:Disulfiram
keywords: breast cancer; cancer stem cells; disulfiram; epithelial-mesenchymal transition