Salinomycin promotes anoikis and decreases the CD44+/CD24- stem-like population via inhibition of STAT3 activation in MDA-MB-231 cells

Hyunsook An, Ji Young Kim, Eunhye Oh, Nahyun Lee, Youngkwan Cho, Jae Hong Seo

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Triple-negative breast cancer (TNBC) is an aggressive tumor subtype with an enriched CD44+/CD24- stem-like population. Salinomycin is an antibiotic that has been shown to target cancer stem cells (CSC); however, the mechanisms of action involved have not been well characterized. The objective of the present study was to investigate the effect of salinomycin on cell death, migration, and invasion, as well as CSC-like properties in MDA-MB-231 breast cancer cells. Salinomycin significantly induced anoikis-sensitivity, accompanied by caspase-3 and caspase-8 activation and PARP cleavage, during anchorage-independent growth. Salinomycin treatment also caused a marked suppression of cell migration and invasion with concomitant downregulation of MMP-9 and MMP-2 mRNA levels. Notably, salinomycin inhibited the formation of mammospheres and effectively reduced the CD44+/CD24- stem-like population during anchorage-independent growth. These observations were associated with the inhibition of STAT3 phosphorylation (Tyr705). Furthermore, interleukin-6 (IL-6)-induced STAT3 activation was strongly suppressed by salinomycin challenge. These findings support the notion that salinomycin may be potentially efficacious for targeting breast cancer stem-like cells through the inhibition of STAT3 activation.

Original languageEnglish
Article numbere0141919
JournalPLoS One
Volume10
Issue number11
DOIs
Publication statusPublished - 2015 Nov 3

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Anoikis
salinomycin
Chemical activation
stems
Neoplastic Stem Cells
Population
breast neoplasms
cells
Stem cells
Matrix Metalloproteinases
Cell Movement
stem cells
Triple Negative Breast Neoplasms
Breast Neoplasms
caspase-8
gelatinase A
Phosphorylation
gelatinase B
cell invasion
Caspase 8

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Salinomycin promotes anoikis and decreases the CD44+/CD24- stem-like population via inhibition of STAT3 activation in MDA-MB-231 cells. / An, Hyunsook; Kim, Ji Young; Oh, Eunhye; Lee, Nahyun; Cho, Youngkwan; Seo, Jae Hong.

In: PLoS One, Vol. 10, No. 11, e0141919, 03.11.2015.

Research output: Contribution to journalArticle

An, Hyunsook ; Kim, Ji Young ; Oh, Eunhye ; Lee, Nahyun ; Cho, Youngkwan ; Seo, Jae Hong. / Salinomycin promotes anoikis and decreases the CD44+/CD24- stem-like population via inhibition of STAT3 activation in MDA-MB-231 cells. In: PLoS One. 2015 ; Vol. 10, No. 11.
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