title: Inhibitory effect of glyceollins on vasculogenesis through suppression of endothelial progenitor cell function.
abstract: METHODS
  Endothelial progenitor cells (EPCs) are derived from hematopoietic stem cells, and have the ability to differentiate into mature endothelial cells and contribute to neovascularization. Glyceollins are a type of phytoalexin produced in soybeans under stress conditions. The aim of this study is to determine the effect of glyceollin treatment on EPCs during early tumor vasculogenesis.
  
  
  RESULTS
  We found that glyceollin treatment significantly decreased the number of EPC colony-forming units in human cord blood-derived AC133⁺ cells and mouse bone-marrow-derived c-Kit⁺/Sca-1⁺/Lin⁻ cells. Glyceollin treatment diminished the number of lineage-committed EPC cells in a dose-dependent manner (1-20 μM). Glyceollin treatment inhibited EPC migration, tube formation and the mRNA expression of angiopoietin-1 (Ang-1), Tie-2, stromal-derived factor-1 (SDF-1), C-X-C-chemokine receptor-4 (CXCR4), and endothelial nitric oxide synthase (eNOS) in cultured EPCs. Glyceollin treatment suppressed activation of Akt, Erk, and eNOS induced by SDF-1α or vascular endothelial growth factor (VEGF). Treatment with 10 mg/kg glyceollins significantly reduced the number of tumor-induced circulating EPCs and the incorporation of EPCs into neovessels in bone marrow transplanted mice.
  
  
  CONCLUSIONS
  These results suggest that glyceollins inhibit the function of EPCs in tumor neovascularization. Glyceollins from soybean elicitation could be beneficial in prevention of cancer development via vasculogenesis.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu, Korea; School of Life Sciences and Biotechnology, Kyungpook National University, Daegu, Korea.
authors.forename: Jin-Hwa
authors.initials: JH
authors.lastname: Choi
authors.forename: Minh Phuong
authors.initials: MP
authors.lastname: Nguyen
authors.forename: Seok-Yun
authors.initials: SY
authors.lastname: Jung
authors.forename: Sang-Mo
authors.initials: SM
authors.lastname: Kwon
authors.forename: Jun-Goo
authors.initials: JG
authors.lastname: Jee
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Lee
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: You-Mie
authors.initials: YM
authors.lastname: Lee
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D036343:Pterocarpans / Q000494:pharmacology*; D042787:Receptor, TIE-2 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013025:Glycine max / Q000737:chemistry; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D010936:Plant Extracts; D036343:Pterocarpans; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; C017343:glyceollin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D042787:Receptor, TIE-2; C079086:Tek protein, mouse; D051057:Proto-Oncogene Proteins c-akt
keywords: Endothelial progenitor cells; Glyceollins; Stromal-derived factor 1; Tumor vasculogenesis; VEGF