Background
Ferroptosis is a therapeutic strategy for breast carcinoma (BC). Solasonine (SS) was linked to ferroptosis as a tumor suppressor. However, whether SS could treat BC by activating ferroptosis and its underlying mechanisms has not been reported.
Conclusion
SS could inactivate the ERK2/MAPK pathway, thereby inducing ferroptosis and further inhibiting BC cell proliferation, migration, and invasion. This study clarified the potential mechanism of SS in BC and provided a theoretical basis for its clinical application.
Methods
We obtained the intersection of genes targeting SS and BC disease through network pharmacology. Bioinformatics analysis revealed that the intersection genes were primarily enriched in the extracellular signal-regulated kinase 2/mitogen-activated protein kinase (ERK2/MAPK) signaling pathway. The interaction modes of SS with ERK2 and epidermal growth factor receptor (EGFR) were simulated by molecular docking. We further detected the expressions of ERK2 and p-ERK2 in BC patients and the correlation between ERK2/p-ERK2 and ferroptosis. The effects and mechanism of SS on ferroptosis in BC were validated by mutation plasmids construction, immunohistology, wound healing, transwell assay, and western blotting using in vitro and in vivo models.
Results
ERK2 and p-ERK2 were up-regulated in BC patients, and the ERK2/p-ERK2 ratio was negatively correlated with ferroptosis. Molecular docking indicated that SS could bind to ERK2 and EGFR to inhibit the activity of the ERK2/MAPK pathway. In vitro and in vivo experiments confirmed that SS induced ferroptosis by inhibiting the ERK2/MAPK pathway, inhibiting proliferation, migration, and invasion of BC cells.