Dandelion extract suppresses the stem-like properties of triple-negative breast cancer cells by regulating CUEDC2/β-catenin/OCT4 signaling axis.

ETHNOPHARMACOLOGICAL RELEVANCE

Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, featuring a high proportion of cancer stem cells (CSCs) and the poorest clinical outcomes. Taraxacum mongolicum Hand. -Mazz., widely recognized as dandelion, is a traditional medicinal herb that has demonstrated promising anti-TNBC potential. However, the efficacy of dandelion in anti-TNBC stem-like properties remains to be elucidated.

AIM OF THE STUDY

The aim was to examine the impact of dandelion extract on the stemness properties of TNBC and to delineate the underlying mechanisms.

MATERIALS AND METHODS

UHPLC-Q-Orbitrap HRMS was employed to characterize the components present in dandelion extract. Network pharmacology was utilized to explore the impact of dandelion-derived compounds on the molecular pathways associated with TNBC. The assessment of TNBC stem-like properties was conducted through mammosphere formation assays and flow cytometry analysis. Western blotting, qRT-PCR, and immunofluorescence were employed to investigate the mechanisms of dandelion extract. 4T1-luc xenograft tumor model was used to assess the anti-tumor effect of dandelion extract in vivo. IVIS imaging technology was used to monitor lung metastasis.

RESULTS

In this study, pharmacological network analysis revealed the potential regulatory effects of dandelion extract on TNBC stemness. Dandelion extract disrupts the stem-like properties in MDA-MB-231 and MDA-MB-468 cell lines via reducing ALDH + cells proportion, impeding mammosphere formation, and downregulating CSC-related markers, including SOX2, SOX9, NANOG, and FOXM1. Furthermore, CUE domain containing protein 2 (CUEDC2) promotes the maintenance of TNBC stemness and contributes to the anti-stemness effects of dandelion extract. Mechanistically, dandelion extract inhibits CUEDC2-mediated nuclear translocation of β-catenin, thereby reducing the transcriptional activity of OCT4. In vivo, dandelion extract suppresses tumor growth, lung metastasis, and decreases the expression of CSC-related markers.

CONCLUSION

These findings suggest that dandelion extract inhibits TNBC stem-like properties via modulating the CUEDC2/β-catenin/OCT4 signaling axis, highlighting its potential as a therapeutic option for TNBC.