Disulfiram suppresses cancer stem-like properties and STAT3 signaling in triple-negative breast cancer cells

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

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14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1069-1076
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume486
Issue number4
DOIs
Publication statusPublished - 2017 May 13

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Keywords

  • ALDH1A1
  • Cancer stem cells
  • Disulfiram
  • Mammosphere
  • STAT3
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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