Sodium ferulate prevents breast cancer metastasis by remodeling the bloodstream microenvironment

  • Eur J Pharmacol. 2026 Jun 25:1030:179092. doi: 10.1016/j.ejphar.2026.179092.
Mengting Lin  1 ,  Shanshan He  2 ,  Chunlian Zhong  3 ,  Weiyu Wang  2 ,  Yinyin Yao  2 ,  Lin Luo  4 ,  Jundan Xu  3 ,  Lei Ma  4 ,  Xinyi Zhao  2 ,  Chengbin Fu  5 ,  Mingqing Huang  6 ,  Yusheng Lu  7
Affiliations
  • 1. Fuzhou Institute of Oceanography, Fujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China; College of Pharmacy, Fujian Key laboratory of Chinese Materia Medical, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China; Department of Pharmacy, Fuzhou Hospital of Traditional Chinese Medicine Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, China.
  • 2. Fuzhou Institute of Oceanography, Fujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China; College of Pharmacy, Fujian Key laboratory of Chinese Materia Medical, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China.
  • 3. Fuzhou Institute of Oceanography, Fujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China.
  • 4. Fuzhou Institute of Oceanography, Fujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China; College of Chemical Engineering, Fuzhou University, Fuzhou, Fujian, 350108, China.
  • 5. Department of Breast Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, Fujian, 350001, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China; Breast Cancer Institute, Fujian Medical University, Fuzhou, Fujian, 350001, China. Electronic address: [email protected].
  • 6. College of Pharmacy, Fujian Key laboratory of Chinese Materia Medical, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China. Electronic address: [email protected].
  • 7. Fuzhou Institute of Oceanography, Fujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China. Electronic address: [email protected].
PMID: 42349818 DOI: 10.1016/j.ejphar.2026.179092
Abstract

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.

Keywords
Bloodstream microenvironment; Cancer metastasis; Cell adhesion; Immune modulation; NF-κB signaling pathway; Sodium ferulate.
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