title: Silibinin, a novel chemokine receptor type 4 antagonist, inhibits chemokine ligand 12-induced migration in breast cancer cells.
abstract: OBJECTIVE
  C-X-C chemokine receptor type 4 (CXCR4) signaling has been demonstrated to be involved in cancer invasion and migration; therefore, CXCR4 antagonist can serve as an anti-cancer drug by preventing tumor metastasis. This study aimed to identify the CXCR4 antagonists that could reduce and/or inhibit tumor metastasis from natural products.
  
  
  RESULTS
  According to the molecular docking screening, we reported here silibinin as a novel CXCR4 antagonist. Biochemical characterization showed that silibinin blocked chemokine ligand 12 (CXCL12)-induced CXCR4 internalization by competitive binding to CXCR4, therefore inhibiting downstream intracellular signaling. In human breast cancer cells MDA-MB-231, which expresses high levels of CXCR4, inhibition of CXCL12-induced chemomigration can be found under silibinin treatment. Overexpression of CXCL12 sensitized MDA-MB-231 cells to the inhibition of silibinin, which was abolished by CXCR4 knockdown. The inhibition of silibinin was also observed in MCF-7/CXCR4 cells rather than MCF-7 cells that express low level of CXCR4.
  
  
  CONCLUSIONS
  Our work demonstrated that silibinin is a novel CXCR4 antagonist that may have potential therapeutic use for prevention of tumor metastasis.
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Liang
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Pan
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Wai-Kit
authors.initials: WK
authors.lastname: Law
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Jian-Shu
authors.initials: JS
authors.lastname: Hu
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Denis Tsz-Ming
authors.initials: DT
authors.lastname: Ip
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Mary Miu-Yee
authors.initials: MM
authors.lastname: Waye
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Tzi-Bun
authors.initials: TB
authors.lastname: Ng
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: chicheongwan@cuhk.edu.hk.
authors.forename: David Chi-Cheong
authors.initials: DC
authors.lastname: Wan
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D012838:Silymarin; D000077385:Silybin
keywords: Breast cancer; CXCR4 antagonist; Chemomigration; Molecular docking; Silibinin