Brucine Inhibits Bone Metastasis of Breast Cancer Cells by Suppressing Jagged1/Notch1 Signaling Pathways

Objective: To examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis. Methods: The osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0.08 mmol/L), or 10 mu mol/L zoledronic acid as positive control. The migration and bone resorption were measured by transwell assay and in vitro bone resorption assay. The protein expressions of Jagged1 and Notch1 were investigated by Western blot. The expressions of transforming growth factor-beta 1 (TGF-beta 1), nuclear factor-kappa B (NF-kappa B) and Hes1 were determined by enzyme-linked immunosorbent assay. Results: Compared with the model group, brucine led to a dose-dependent decrease on migration of MDA-MB-231 cells, inhibited RANKL-induced osteoclastogenesis and bone resorption of RAW264.7 cells (P < 0.01). Furthermore, brucine decreased the protein levels of Jagged1 and Notch1 in MDA-MB-231 cells and RAW264.7 cells co-cultured system as well as the expressions of TGF-beta 1, NF-kappa B and Hes1 (P < 0.05 or P < 0.01). Conclusion: Brucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.