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


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-?B, and reduced extracellular IL-8 levels in mammospheres. Knocking down NF-?B expression using a p65-specific siRNA reduced CSC formation and secreted IL-8 levels in mammospheres. Sulconazole reduced nuclear NF-?B protein levels and secreted IL-8 levels in mammospheres. These new findings show that sulconazole blocks the NF-?B/IL-8 signaling pathway and CSC formation. NF-?B/IL-8 signaling is important for CSC formation and may be an important therapeutic target for BCSC treatment.

SUBMITTER: Choi HS 

PROVIDER: S-EPMC6770215 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Choi Hack Sun HS   Kim Ji-Hyang JH   Kim Su-Lim SL   Lee Dong-Sun DS  

Cells 20190830 9


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<sup>high</sup>/CD24<sup>low</sup>) as well as the expression of another CSC  ...[more]

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