Abstract

Ethnopharmacological relevance Triple-negative breast cancer (TNBC) has a poor clinical prognosis and shows resistance to traditional treatments. Ferroptosis is a potential therapeutic strategy for TNBC. Although dandelion extract has demonstrated anti-tumor effects against TNBC, its role in regulating ferroptosis has not been elucidated. Aim of the study This study aimed to investigate the role and mechanisms of dandelion extract in inhibiting TNBC via the induction of ferroptosis. Materials and methods Cell viability and cell death were detected by CCK-8 assay and PI/Hoechst 33342 dual staining, respectively. Proteomic profiling was used to identify the mechanisms of dandelion extract-induced cell death. Ferroptosis was assessed by measuring key hallmarks, including Fe 2+ accumulation, lipid peroxidation, mitochondrial dysfunction, and ultrastructural changes. Mechanistic validation was achieved through target-specific interference and subsequent biomolecular analysis. Results Dandelion extract selectively induced cell death in TNBC cells without affecting normal MCF-10A cells. Proteomic and experimental evidence indicates that dandelion extract induces ferroptosis in TNBC cells, characterized by elevated Fe 2+ , ROS, lipid peroxidation, MDA levels, and mitochondrial dysfunction. Crucially, ferroptosis inhibitors attenuated the inhibitory effect of dandelion extract on TNBC cell viability, confirming ferroptosis as the primary cell death mechanism. Mechanistic studies have demonstrated that dandelion extract promoted ferroptosis in TNBC cells both in vitro and in vivo through NCOA4-mediated ferritinophagy. Conclusions This study demonstrates that dandelion extract induces ferroptosis in TNBC cells both in vitro and i n vivo by regulating ferritinophagy mediated by the NCOA4-FTH1 axis, thus suggesting novel therapeutic strategies for TNBC treatment.