1. Ebastine impairs metastatic spread in triple-negative breast cancer by targeting focal adhesion kinase.
- Author
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Seo, Juyeon, Park, Minsu, Ko, Dongmi, Kim, Seongjae, Park, Jung Min, Park, Soeun, Nam, Kee Dal, Farrand, Lee, Yang, Jinsol, Seok, Chaok, Jung, Eunsun, Kim, Yoon-Jae, Kim, Ji Young, and Seo, Jae Hong
- Abstract
We sought to investigate the utility of ebastine (EBA), a second-generation antihistamine with potent anti-metastatic properties, in the context of breast cancer stem cell (BCSC)-suppression in triple-negative breast cancer (TNBC). EBA binds to the tyrosine kinase domain of focal adhesion kinase (FAK), blocking phosphorylation at the Y397 and Y576/577 residues. FAK-mediated JAK2/STAT3 and MEK/ERK signaling was attenuated after EBA challenge in vitro and in vivo. EBA treatment induced apoptosis and a sharp decline in the expression of the BCSC markers ALDH1, CD44 and CD49f, suggesting that EBA targets BCSC-like cell populations while reducing tumor bulk. EBA administration significantly impeded BCSC-enriched tumor burden, angiogenesis and distant metastasis while reducing MMP-2/-9 levels in circulating blood in vivo. Our findings suggest that EBA may represent an effective therapeutic for the simultaneous targeting of JAK2/STAT3 and MEK/ERK for the treatment of molecularly heterogeneous TNBC with divergent profiles. Further investigation of EBA as an anti-metastatic agent for the treatment of TNBC is warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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