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

doi:10.1016/j.canlet.2016.11.022

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

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

29 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 language	English
Pages (from-to)	151-160
Number of pages	10
Journal	Cancer letters
Volume	386
DOIs	https://doi.org/10.1016/j.canlet.2016.11.022
Publication status	Published - 2017 Feb 1

Bibliographical note

Funding 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 .

Publisher Copyright:
© 2016 Elsevier Ireland Ltd

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

Anoikis
Apoptosis
Calpain
Disulfiram
Metastasis
Triple-negative breast cancer

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2016.11.022

Cite this

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

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.",

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author = "Kim, {Ji Young} and Nahyun Lee and Kim, {Yoon Jae} and Youngkwan Cho and Hyunsook An and Eunhye Oh and Cho, {Tae Min} and Daeil Sung and Seo, {Jae Hong}",

note = "Funding 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 . Publisher Copyright: {\textcopyright} 2016 Elsevier Ireland Ltd Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",

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AU - Kim, Ji Young

AU - Lee, Nahyun

AU - Kim, Yoon Jae

AU - Cho, Youngkwan

AU - An, Hyunsook

AU - Oh, Eunhye

AU - Cho, Tae Min

AU - Sung, Daeil

AU - Seo, Jae Hong

N1 - Funding 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 . Publisher Copyright: © 2016 Elsevier Ireland Ltd Copyright: Copyright 2017 Elsevier B.V., All rights reserved.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

KW - Anoikis

KW - Apoptosis

KW - Calpain

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KW - Metastasis

KW - Triple-negative breast cancer

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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