title: Oligomannurarate sulfate inhibits CXCL12/SDF-1-mediated proliferation and invasion of human tumor cells in vitro.
abstract: OBJECTIVE
  JG6 is a novel marine-derived oligosaccharide that has shown to inhibit angiogenesis and tumor metastasis. In this study, we sought to identify the potential target responsible for the anti-cancer activity of JG6.
  
  
  METHODS
  Human liver cancer cell line Bel-7402 and human cervical cancer cell line HeLa were examined. CXCL12-stimulated cell proliferation and migration were determined using a CCK-8 kit and a transwell assay, respectively. Western blotting was performed to examine the changes in CXCL12/CXCR4 axis. Molecular docking and surface plasmon resonance (SPR) were performed to characterize the possible interaction between JG6 and the CXCL12/CXCR4 axis.
  
  
  RESULTS
  Treatment with CXCL12 potently stimulated the proliferation and migration in both Bel-7402 and HeLa cells. Co-treatment of the cells with JG6 (10, 50 and 100 μg/mL) dose-dependently impeded the CXCL12-stimulated cell proliferation and migration. Furthermore, CXCL12 rapidly induced phosphorylation of AKT, ERK, FAK and Paxillin in Bel-7402 and HeLa cells, whereas pretreatment with JG6 dose-dependently inhibited the CXCL12-induced phosphorylation of these proteins. The SPR assay showed that JG6 bound to CXCL12 with a high affinity. In molecular docking study, JG6 appeared to interact with CXCL12 via multiple polar interactions, including 6 ionic bonds and 7 hydrogen bonds.
  
  
  CONCLUSIONS
  Inhibition of the CXCL12/CXCR4 axis by JG6 may account for its anticancer activity.
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, China.
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Wen
authors.forename: Shao
authors.initials: S
authors.lastname: Xie
authors.forename: Xian-liang
authors.initials: XL
authors.lastname: Xin
authors.forename: Mei-yu
authors.initials: MY
authors.lastname: Geng
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008351:Mannans / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D020349:Surface Plasmon Resonance; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D008351:Mannans; D009363:Neoplasm Proteins; C524388:oligomannurarate sulfate