Background/aim: Breast cancer stem cells (BCSCs) are a subpopulation of tumor cells that play a role in therapeutic resistance. In this study, we demonstrated that sertaconazole, an antifungal agent, displayed a potent inhibition on cancer stem cells (CSCs) and investigated the mechanism of action involved in its anti-BCSC effect.
Materials and methods: The effect of sertaconazole on BCSCs was investigated using a mammosphere formation assay, a colony formation assay, and a cell migration assay. In addition, CD44high/CD24low and ALDEFLOR analyses, an apoptosis assay, quantitative real-time PCR, western blotting, an electrophoretic mobility shift assay, and a cytokine profiling assay were performed.
Results: Sertaconazole inhibited cell proliferation, colony formation, cell migration, mammosphere formation, and mammosphere proliferation. It also induced apoptosis of breast cancer cells. It decreased the subpopulation of CD44high/CD24low and aldehyde dehydrogenase-expressing cells. It also reduced the DNA binding of Stat3 and nuclear protein expression levels of phosphorylated Stat3. Furthermore, it reduced the IL-8 mRNA levels of the mammosphere.
Conclusion: Sertaconazole can inhibit the Stat3 and IL-8 signaling pathways and induce CSC death. Thus, sertaconazole might be a potential inhibitor of BCSCs.
Keywords: Breast cancer stem cells; IL-8; Sertaconazole; Stat3.
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