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Scutellaria Barbata Water Extract Suppresses Breast Cancer Growth and Lung Metastasis by Inducing Ferroptosis
Quanyang Liao1, Yutong Wang1, Xiaoyue Li1
1Yunnan University of Chinese Medicine, Kunming, China.
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.
Insights
Scutellaria barbata water extract (SBW) effectively combats breast cancer lung metastasis by inducing ferroptosis and inhibiting epithelial-mesenchymal transition (EMT). Arachidonic acid is identified as a key component mediating these antimetastatic effects.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Lung metastasis is a major cause of mortality in aggressive breast cancers, especially triple-negative breast cancer (TNBC).
- Effective antimetastatic strategies are urgently needed for TNBC treatment.
- Targeting metastasis pathways is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the efficacy and safety of Scutellaria barbata water extract (SBW) against breast cancer lung metastasis.
- To elucidate the molecular mechanisms of SBW, focusing on ferroptosis induction and epithelial-mesenchymal transition (EMT) inhibition.
- To identify key bioactive components responsible for SBW's antimetastatic effects.
Main Methods:
- In vitro and in vivo experiments assessed SBW's antitumor and antimetastatic activities.
- Proteomic and metabolomic analyses identified key pathways and bioactive components.
- Ferroptosis markers and EMT-related proteins were quantified; arachidonic acid (AA) was validated.
Main Results:
- SBW reduced breast cancer cell viability, migration, and invasion in vitro.
- SBW suppressed tumor growth and lung metastasis in vivo without toxicity.
- SBW induced ferroptosis (via GPX4 inhibition) and inhibited EMT (via Twist/N-cadherin downregulation), with AA identified as a key mediator.
Conclusions:
- SBW demonstrates potent antimetastatic effects against breast cancer lung metastasis.
- Dual mechanisms of ferroptosis induction and EMT inhibition contribute to SBW's efficacy.
- Arachidonic acid is a critical bioactive component mediating ferroptosis and antimetastatic activity.