title: Disulfiram induces anoikis and suppresses lung colonization in triple-negative breast cancer via calpain activation.
abstract: Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype. Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence, but has also been shown to kill TNBC cells in a copper (Cu)-dependent manner. Exactly how this occurs has not been clearly elucidated. We sought to investigate the mechanisms responsible for DSF/Cu-dependent induction of apoptosis and suppression of lung colonization by TNBC cells. DSF/Cu induced anoikis and significantly suppressed cell migration and invasion with negative effects on focal adhesions, coinciding with vimentin breakdown and calpain activation in TNBC cells. In a xenograft tumor model, DSF suppressed tumor growth and lung nodule growth, which was also associated with calpain activation. These findings warrant further investigation of disulfiram as a potential treatment for metastatic TNBC.
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; 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: Youngkwan
authors.initials: Y
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.
authors.forename: Hyunsook
authors.initials: H
authors.lastname: An
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: 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.
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. Electronic address: cancer@korea.ac.kr.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Seo
mesh_terms: D000818:Animals; D023102:Anoikis / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002154:Calpain / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004221:Disulfiram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D022001:Focal Adhesions / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000517:prevention & control* / Q000556:secondary; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D059748:Proteolysis; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D014746:Vimentin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D014746:Vimentin; D003300:Copper; D002154:Calpain; C029892:cupric chloride; D004221:Disulfiram
keywords: Anoikis; Apoptosis; Calpain; Disulfiram; Metastasis; Triple-negative breast cancer