Salinomycin possesses anti-tumor activity and inhibits breast cancer stem-like cells via an apoptosis-independent pathway

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

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cancer stem cells (CSCs) play important roles in the formation, growth and recurrence of tumors, particularly following therapeutic intervention. Salinomycin has received recent attention for its ability to target breast cancer stem cells (BCSCs), but the mechanisms of action involved are not fully understood. In the present study, we sought to investigate the mechanisms responsible for salinomycin's selective targeting of BCSCs and its anti-tumor activity. Salinomycin suppressed cell viability, concomitant with the downregulation of cyclin D1 and increased p27kip1 nuclear accumulation. Mammosphere formation assays revealed that salinomycin suppresses self-renewal of ALDH1-positive BCSCs and downregulates the transcription factors Nanog, Oct4 and Sox2. TUNEL analysis of MDA-MB-231-derived xenografts revealed that salinomycin administration elicited a significant reduction in tumor growth with a marked downregulation of ALDH1 and CD44 levels, but seemingly without the induction of apoptosis. Our findings shed further light on the mechanisms responsible for salinomycin's effects on BCSCs.

Original languageEnglish
Pages (from-to)696-703
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume466
Issue number4
DOIs
Publication statusPublished - 2015 Oct 30

Keywords

  • ALDH1
  • Breast cancer stem cells
  • Mammosphere
  • Salinomycin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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