Unveiling 8,12‐dimethoxysanguinarine: A Potent Inhibitor of Breast Cancer Metastasis via FN1 Downregulation

This study investigated the effects of 8,12‐dimethoxysanguinarine (DSG) from Eomecon chionantha Hance on the malignant biological activity of breast cancer cells. RNA‐sequencing measure analysis revealed that metastasis‐related genes were significantly downregulated in DSG‐treated MCF‐7 cells. DSG significantly inhibits the migration ability in MCF‐7 cells. Molecular docking studies demonstrated significant interactions between DSG and the FN1 protein, with a binding energy of ‐8.91 Kcal/mol. Additionally, FN1 mRNA expression was significantly upregulated in 1,085 breast tumor samples compared to normal tissue in the TCGA‐BRCA dataset. DSG also suppressed MCF‐7 cell metastasis by downregulating FN1 expression. Furthermore, DSG was identified as a promising candidate based on ADMET and drug‐likeness assessments. Combination studies indicated that DSG synergized with the conventional chemotherapeutic agent doxorubicin to suppress MCF‐7 cell migration, as confirmed by wound‐healing and transwell assays. Collectively, these findings suggest that DSG may serve as a potential agent for inhibiting breast cancer cell metastasis by decreasing FN1 expression.