Scutellaria Barbata Water Extract Suppresses Breast Cancer Growth and Lung Metastasis by Inducing Ferroptosis

Background: Lung metastasis is the primary cause of mortality in aggressive breast cancers, particularly triple-negative breast Cancer (TNBC), underscoring the urgent need for effective antimetastatic strategies.

Objective: This study aimed to evaluate the efficacy, safety, and molecular mechanisms of Scutellaria barbata water extract (SBW) against breast Cancer lung metastasis, with a focus on Ferroptosis induction and epithelial-mesenchymal transition (EMT) inhibition.

Methods: In vitro and in vivo experiments to evaluate the antitumor and antimetastatic activities of SBW. Proteomic and metabolomic analyses were performed to identify key pathways and bioactive components. Ferroptosis markers and EMT-related proteins were measured by biochemical assays and Western blotting. Arachidonic acid (AA) was validated using in vitro and in vivo functional experiments.

Results: SBW dose-dependently reduced breast Cancer cell viability, migration, and invasion in vitro. In vivo, SBW suppressed tumor growth and lung metastasis in 4T1 tumor-bearing mice without systemic toxicity. Proteomic analysis revealed that SBW induced Ferroptosis, characterized by increased Fe²⁺, ROS, LPO levels, and upregulation of HO-1/NCOA4, concomitant with downregulation of GPX4. SBW also inhibited EMT by reducing Twist and N-Cadherin expression without affecting E-cadherin. Metabolomic profiling identified AA as a critical bioactive component. Functional validation confirmed that AA induced Ferroptosis in vitro and inhibited tumor growth/metastasis in vivo.

Conclusions: SBW exerts potent antimetastatic effects through dual mechanisms: induction of Ferroptosis via GPX4 inhibition and suppression of EMT via Twist/N-Cadherin downregulation. Arachidonic acid plays a central role in mediating Ferroptosis.