Unveiling 8,12‐Dimethoxysanguinarine: A Potent Inhibitor of Breast Cancer Metastasis via Fibronectin 1 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 Fibronectin 1 (FN1) protein, with a binding energy of -8.91 kcal/mol. Additionally, FN1 messenger RNA expression was significantly upregulated in 1085 breast tumor samples compared to normal tissue in the Cancer Genome Atlas Breast Invasive Carcinoma Collection dataset. DSG also suppressed MCF-7 cell metastasis by downregulating FN1 expression. Furthermore, DSG was identified as a promising candidate based on absorption distribution metabolism excretion toxicity 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.