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Br J Cancer. 2013 Nov 12;109(10):2587-96. doi: 10.1038/bjc.2013.642. Epub 2013 Oct 15.

Silencing NOTCH signaling causes growth arrest in both breast cancer stem cells and breast cancer cells.

Author information

1
Department of Biomedical Sciences, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.

Abstract

BACKGROUND:

Breast cancer stem cells (BCSCs) are characterized by high aldehyde dehydrogenase (ALDH) enzyme activity and are refractory to current treatment modalities, show a higher risk for metastasis, and influence the epithelial to mesenchymal transition (EMT), leading to a shorter time to recurrence and death. In this study, we focused on examination of the mechanism of action of a small herbal molecule, psoralidin (Pso) that has been shown to effectively suppress the growth of BSCSs and breast cancer cells (BCCs), in breast cancer (BC) models.

METHODS:

ALDH(-) and ALDH(+) BCCs were isolated from MDA-MB-231 cells, and the anticancer effects of Pso were measured using cell viability, apoptosis, colony formation, invasion, migration, mammosphere formation, immunofluorescence, and western blot analysis.

RESULTS:

Psoralidin significantly downregulated NOTCH1 signaling, and this downregulation resulted in growth inhibition and induction of apoptosis in both ALDH(-) and ALDH(+) cells. Molecularly, Pso inhibited NOTCH1 signaling, which facilitated inhibition of EMT markers (β-catenin and vimentin) and upregulated E-cadherin expression, resulting in reduced migration and invasion of both ALDH(-) and ALDH(+) cells.

CONCLUSION:

Together, our results suggest that inhibition of NOTCH1 by Pso resulted in growth arrest and inhibition of EMT in BCSCs and BCCs. Psoralidin appears to be a novel agent that targets both BCSCs and BCCs.

PMID:
24129237
PMCID:
PMC3833225
DOI:
10.1038/bjc.2013.642
[Indexed for MEDLINE]
Free PMC Article

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