2025 CONVENTION
Bupleurum falcatum root extract attenuates stress-driven cancer metastasis via inhibition of Src kinase activation
Bupleurum falcatum (BF) root has long been used in herbal medicine to relieve stress-related symptoms. Here, we investigated the anti-metastatic potential of its ethanolic extract (EBF) under chronic psychological stress and explored the underlying mechanisms. Cancer cell motility was measured by Transwell migration and invasion assays, and a murine lung metastasis model was established using chronic unpredictable stress stimuli. Network pharmacology and pathway enrichment analyses were performed to identify candidate molecular targets. EBF markedly inhibited catecholamine-induced migration and invasion of MDA-MB-231 breast cancer and Hep3B hepatocellular carcinoma cells, and significantly reduced stress-driven lung metastasis of 4T1 breast cancer cells in vivo. Mechanistically, Src kinase was identified as a central regulatory node, and Western blotting confirmed that EBF decreased Src phosphorylation. Saikosaponin A and D, major constituents of EBF, similarly suppressed adrenergic agonist-induced cancer cell migration, with molecular docking suggesting direct interaction with the Src kinase domain. Collectively, these findings demonstrate that EBF suppresses stress-associated cancer metastasis by targeting Src signaling, highlighting its promise as a therapeutic agent for metastasis promoted by chronic stress.