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.
Bibliographical noteFunding Information:
We thank Lee Farrand for editing the manuscript. This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) , funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI12C1852 ), the National Research Foundation of Korea (NRF) grant, funded by the Ministry of Science, ICT & Future Planning (MSIP, grant number: 2015R1C1A2A01053747 ), and supported by the Korea University Guro Hospital Grant ( O1600121 ) and the Brain Korea (BK) 21 Plus Program .
© 2016 Elsevier Ireland Ltd
Copyright 2017 Elsevier B.V., All rights reserved.
- Triple-negative breast cancer
ASJC Scopus subject areas
- Cancer Research