Disulfiram induces anoikis and suppresses lung colonization in triple-negative breast cancer via calpain activation

Ji Young Kim, Nahyun Lee, Yoon Jae Kim, Youngkwan Cho, Hyunsook An, Eunhye Oh, Tae Min Cho, Daeil Sung, Jae Hong Seo

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)151-160
Number of pages10
JournalCancer Letters
Volume386
DOIs
Publication statusPublished - 2017 Feb 1

Keywords

  • Anoikis
  • Apoptosis
  • Calpain
  • Disulfiram
  • Metastasis
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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