Flubendazole elicits anti-metastatic effects in triple-negative breast cancer via STAT3 inhibition

Eunhye Oh, Yoon Jae Kim, Hyunsook An, Daeil Sung, Tae Min Cho, Lee Farrand, Seojin Jang, Jae Hong Seo, Ji Young Kim

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Tumor metastasis remains the cause of 90% of cancer-related deaths. Cancer stem cells (CSC) are thought to be responsible for the aggressive and metastatic nature of triple-negative breast cancers (TNBC), and new therapeutic strategies are being devised to target them. Flubendazole (FLU) is a widely used anthelmintic agent that also exhibits anticancer activity in several cancer types. The aim of this study was to characterize the mechanism of action of FLU on breast cancer stem cell (BCSC)-like properties and metastasis in TNBC. FLU treatment caused a significant induction of apoptosis, accompanied by G2/M phase accumulation, caspase-3/-7 activation and the dysregulation of STAT3 activation in TNBC cells. The latter phenomenon was associated with impairment of cancer stem-like traits, concomitant with a reduction in the CD24low/CD44high, CD24high/CD49fhigh subpopulation, ALDH1 activity and mammosphere formation. The BCSC-enriched populations exhibited enhanced metastasis with higher STAT3 activation, while FLU administration inhibited tumor growth, angiogenesis and lung and liver metastasis, coinciding with decreased MMP-2 and MMP-9 levels in circulating blood. FLU kills not only rapid proliferating tumor cells but also effectively eradicates BCSC-like cells in vitro and in vivo. Our findings warrant further investigation of FLU as a treatment for metastatic TNBC.

Original languageEnglish
JournalInternational Journal of Cancer
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Keywords

  • Cancer stem cells
  • Flubendazole
  • Metastasis
  • STAT3
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Flubendazole elicits anti-metastatic effects in triple-negative breast cancer via STAT3 inhibition'. Together they form a unique fingerprint.

  • Cite this