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

Xinxin Deng; Yanna Jiao; Huifeng Hao; Zhengwang Guo; Guo An; Wenlong Zhang; Dong Xue; Shuyan Han

doi:10.1016/j.jep.2025.119408

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

J Ethnopharmacol. 2025 Jan 24:342:119408. doi: 10.1016/j.jep.2025.119408. Online ahead of print.

Authors

Xinxin Deng¹, Yanna Jiao², Huifeng Hao², Zhengwang Guo¹, Guo An³, Wenlong Zhang³, Dong Xue⁴, Shuyan Han⁵

Affiliations

¹ Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Department of Integration of Chinese and Western Medicine, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, 100142, China.
² Department of Integration of Chinese and Western Medicine, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, 100142, China.
³ Department of Laboratory Animal, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, 100142, China.
⁴ Department of Integration of Chinese and Western Medicine, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, 100142, China. Electronic address: dong.xue@bjmu.edu.cn.
⁵ Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Department of Integration of Chinese and Western Medicine, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, 100142, China. Electronic address: shuyanhan@bjmu.edu.cn.

PMID: 39864604
DOI: 10.1016/j.jep.2025.119408

Abstract

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.

Keywords: CUEDC2; Cancer stem cell; Dandelion extract; Triple-negative breast cancer.