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Flubendazole elicits anti‐metastatic effects in triple‐negative breast cancer via STAT3 inhibition
Author(s) -
Oh Eunhye,
Kim YoonJae,
An Hyunsook,
Sung Daeil,
Cho TaeMin,
Farrand Lee,
Jang Seojin,
Seo Jae Hong,
Kim Ji Young
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31585
Subject(s) - metastasis , triple negative breast cancer , cancer stem cell , angiogenesis , breast cancer , cancer research , cancer , medicine , metastatic breast cancer , stem cell , lung cancer , immunology , biology , oncology , genetics
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 CD24 low /CD44 high , CD24 high /CD49f high 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.