期刊
CELLS
卷 8, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/cells8091007
关键词
sulconazole; NF-kappa B; IL-8; mammosphere; breast cancer stem cells
类别
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2016R1A6A1A03012862, NRF-2019R1H1A2039751]
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-kappa B, and reduced extracellular IL-8 levels in mammospheres. Knocking down NF-kappa B expression using a p65-specific siRNA reduced CSC formation and secreted IL-8 levels in mammospheres. Sulconazole reduced nuclear NF-kappa B protein levels and secreted IL-8 levels in mammospheres. These new findings show that sulconazole blocks the NF-kappa B/IL-8 signaling pathway and CSC formation. NF-kappa B/IL-8 signaling is important for CSC formation and may be an important therapeutic target for BCSC treatment.
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