title: Brucine inhibits bone metastasis of breast cancer cells by suppressing Jagged1/Notch1 signaling pathways.
abstract: 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 μmol/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-β1 (TGF-β1), nuclear factor-kappa B (NF-κB) 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-β1, NF-κB and Hes1 (P<0.05 or P<0.01).
  
  
  CONCLUSIONS
  Brucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.
authors.affiliation: Beijing University of Chinese Medicine, Beijing, 100029, China.
authors.forename: Ke-Fei
authors.initials: KF
authors.lastname: Hu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Xiang-Ying
authors.initials: XY
authors.lastname: Kong
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Mi-Cun
authors.initials: MC
authors.lastname: Zhong
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Hong-Ye
authors.initials: HY
authors.lastname: Wan
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lin
authors.affiliation: Department of Scientific Research and Education, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, China. 746602479@qq.com.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Pei
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D000072100:Jagged-1 Protein / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D051881:Receptor, Notch1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013331:Strychnine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000072100:Jagged-1 Protein; D051881:Receptor, Notch1; C083806:brucine; D013331:Strychnine
keywords: Jagged1/Notch1 signaling pathway; bone metastasis; breast cancer; brucine