کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525556 1546683 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticleDisulfiram induces anoikis and suppresses lung colonization in triple-negative breast cancer via calpain activation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ArticleDisulfiram induces anoikis and suppresses lung colonization in triple-negative breast cancer via calpain activation
چکیده انگلیسی


- Antitumor activity of disulfiram occurs in a copper-dependent manner.
- Disulfiram elicits anti-migratory and anti-invasive effects in TNBC.
- Disulfiram induces focal adhesion loss and cytoskeletal collapse.
- Calpain activation is involved in disulfiram-induced anoikis.
- Disulfiram suppresses tumor growth and lung colonization in vivo.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 386, 1 February 2017, Pages 151-160
نویسندگان
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