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

Cells. 2019 Aug 30;8(9):1007. doi: 10.3390/cells8091007.


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 (CD44high/CD24low) 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.

Keywords: IL-8; NF-κB; breast cancer stem cells; mammosphere; sulconazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Carcinogenesis / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Imidazoles / pharmacology*
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / metabolism
  • MCF-7 Cells
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Transcription Factor RelA / antagonists & inhibitors*
  • Transcription Factor RelA / metabolism


  • CXCL8 protein, human
  • Imidazoles
  • Interleukin-8
  • Transcription Factor RelA
  • sulconazole