Disruption of the NF-κB/IL-8 Signaling Axis by Sulconazole Inhibits Human Breast Cancer Stem Cell Formation

Breast Cancer Stem Cells (BCSCs) are tumor-initiating cells that possess the capacity for self-renewal. Cancer Stem Cells (CSCs) are responsible for poor outcomes caused by therapeutic resistance. In our study, we found that sulconazole-an Antifungal medicine in the imidazole class-inhibited cell proliferation, tumor growth, and CSC formation. This compound also reduced the frequency of cells expressing CSC markers (CD44^high/CD24^low) as well as the expression of another CSC marker, aldehyde dehydrogenase (ALDH), and Other self-renewal-related genes. Sulconazole inhibited mammosphere formation, reduced the protein level of nuclear NF-κB, and reduced extracellular IL-8 levels in mammospheres. Knocking down NF-κB expression using a p65-specific siRNA reduced CSC formation and secreted IL-8 levels in mammospheres. Sulconazole reduced nuclear NF-κB protein levels and secreted IL-8 levels in mammospheres. These new findings show that sulconazole blocks the NF-κB/IL-8 signaling pathway and CSC formation. NF-κB/IL-8 signaling is important for CSC formation and may be an important therapeutic target for BCSC treatment.