Sodium ferulate prevents breast cancer metastasis by remodeling the bloodstream microenvironment.

Metastasis remains the leading cause of mortality in breast cancer, and effective prevention strategies are urgently needed. Sodium ferulate (SF), a bioactive compound derived from ferulic acid, has demonstrated diverse pharmacological activities, yet its role in suppressing cancer metastasis remains unclear. In this study, we demonstrate that SF significantly inhibits breast cancer metastasis through comprehensive modulation of the bloodstream microenvironment. At non-toxic concentrations, SF inhibited the migration and invasion of MCF-7 and MDA-MB-231 cells by suppressing the BMP4/Smad1/5/9 signaling pathway, reversing epithelial-mesenchymal transition (EMT), and disrupting cell cycle progression. SF also enhanced the sensitivity of breast cancer cells to paclitaxel. In addition, SF reduced tumor cell adhesion to endothelial cells by blocking TNF-α-induced expression of ICAM-1 and VCAM-1 through inhibition of NF-κB signaling cascade. Furthermore, SF attenuated platelet activation and angiogenesis, two key processes involved in metastatic dissemination and colonization. In 4T1 mouse metastasis model, SF treatment significantly decreased pulmonary metastatic nodules without causing organ toxicity. Immunohistochemical analysis further confirmed decreased expression of BMP4, PI3K, and N-cadherin in lung tissues following SF treatment. Additionally, SF enhanced systemic immunity by increasing the proportion of cytotoxic T cells and natural killer cells in peripheral blood. Collectively, these findings reveal that SF exerts potent anti-metastatic effects by modulating tumor-bloodstream-immune interactions rather than direct cytotoxicity. By remodeling the bloodstream microenvironment and enhancing immune defense, SF may represent a promising and safe candidate for the prevention of breast cancer metastasis.