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

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.
Hack Sun Choi 1 2,  Ji-Hyang Kim 3,  Su-Lim Kim 1 3,  Dong-Sun Lee 4 5 6
Affiliations

Affiliations

  • 1 School of Biomaterials Sciences and Technology, College of Applied Life Science, Jeju National University, Jeju 63243, Korea.
  • 2 Subtropical/tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea.
  • 3 Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Korea.
  • 4 School of Biomaterials Sciences and Technology, College of Applied Life Science, Jeju National University, Jeju 63243, Korea. dongsunlee@jejunu.ac.kr.
  • 5 Subtropical/tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea. dongsunlee@jejunu.ac.kr.
  • 6 Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Korea. dongsunlee@jejunu.ac.kr.
PMID: 31480284 DOI: 10.3390/cells8091007
Abstract

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.

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