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

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.