Sertaconazole, an Imidazole Antifungal Agent, Suppresses the Stemness of Breast Cancer Cells by Inhibiting Stat3 Signaling.

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, CD44/CD24 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 CD44/CD24 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.