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

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kim YJ,Kim JY,Lee N,Oh E,Sung D,Cho TM,Seo JH

doi

10.1016/j.bbrc.2017.03.164

subject

Has Abstract

pub_date

2017-05-13 00:00:00

pages

1069-1076

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(17)30642-3

journal_volume

486

pub_type

杂志文章

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