title: Berberine inhibits the proliferation and migration of breast cancer ZR-75-30 cells by targeting Ephrin-B2.
abstract: BACKGROUND
  Berberine, a plant-derived compound isolated from Coptis chinensis used in traditional Chinese medicine, has been shown to possess anti-cancer properties. However, no study has shown that berberine could target ephrin-B2, which plays a critical role in cell proliferation and migration.
  
  
  OBJECTIVE
  The aim of this study is to investigate the effect of berberine on cancer cell growth and migration, through the regulation of ephrin-B2 and downstream signaling molecules.
  
  
  METHODS
  In this study, a high ephrin-B2-expressing cell membrane chromatography method was developed to investigate 48 crude extracts from traditional Chinese medicine that could act on ephrin-B2. Cell proliferative and wound-healing assays were used to study the effect of berberine on cancer cell growth and migration. The mechanism of berberine was investigated using western blot.
  
  
  RESULTS
  Berberine was isolated from C. chinensis extracts and showed activity on the HEK293/ephrin-B2 cell membrane chromatography column. Berberine showed a greater inhibitory effect in high-expressing ephrin-B2 cells (HEK293/ephrin-B2 cells) than in normal HEK293 cells, and decreased the expression of ephrin-B2 and its PDZ binding proteins, which indicates that ephrin-B2 is a target of berberine. Furthermore, berberine downregulates the phosphorylation of VEGFR2 and downstream signaling members (AKT and Erk1/2), which in turn downregulates the expression of MMP2 and MMP9.
  
  
  CONCLUSIONS
  The above data confirm the inhibitory effects of berberine on ZR-75-30 cell proliferation and cell migration. Overall, our studies demonstrate that berberine inhibits cell growth and migration by targeting ephrin-B2.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta Weststreet, #54, Xi'an, Shaanxi Province 710061, PR China.
authors.forename: Weina
authors.initials: W
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta Weststreet, #54, Xi'an, Shaanxi Province 710061, PR China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta Weststreet, #54, Xi'an, Shaanxi Province 710061, PR China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta Weststreet, #54, Xi'an, Shaanxi Province 710061, PR China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta Weststreet, #54, Xi'an, Shaanxi Province 710061, PR China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta Weststreet, #54, Xi'an, Shaanxi Province 710061, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta Weststreet, #54, Xi'an, Shaanxi Province 710061, PR China. Electronic address: zhang2008@mail.xjtu.edu.cn.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D039323:Coptis / Q000737:chemistry*; D036388:Ephrin-B2 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D036388:Ephrin-B2; D010936:Plant Extracts; D001599:Berberine
keywords: Berberine; Breast cancer; Cell growth; Cell migration; Ephrin-B2