title: Pristimerin Inhibits Prostate Cancer Bone Metastasis by Targeting PC-3 Stem Cell Characteristics and VEGF-Induced Vasculogenesis of BM-EPCs.
abstract: OBJECTIVE
  Prostate cancer (PCa) is one of the most common malignant cancers and a major leading cause of cancer deaths in men. Cancer stem-like cells are shown to be highly tumorigenic, pro-angiogenic and can significantly contribute to tumor new vessel formation and bone marrow derived-EPCs (BM-EPCs) are shown to recruit to the angiogenic switch in tumor growth and metastatic progression, suggesting the importance of targeting cancer stem cells (CSCs) and EPCs for novel tumor therapies. Pristimerin, an active component isolated from Celastraceae and Hippocrateaceae, has shown anti-tumor effects in some cell lines in previous studies. However, the effect and mechanism of Pristimerin on CSCs and EPCs in PCa bone metastasis are not well studied.
  
  
  METHODS
  The effect of Pristimerin on PC-3 stem cell characteristics and metastasis were detected by spheroid formation, CD133 and CD44 protein expression, matrix-gel invasive assay and colony-formation assay in vitro, VEGF and pro-inflammatory cytokines expression by ELISA assay, and tumor tumorigenicity by X-ray and MR in NOD-SCID mice model in vivo. In addition, we also detected the effect of Pristimerin on VEGF-induced vasculogenesis and protein expression of BM-EPCs.
  
  
  RESULTS
  Pristimerin could significantly inhibit spheroid formation and protein expression of CD133 and CD44, reduce VEGF and pro-inflammation cytokines expression of PC-3 cell, and prevent the xenografted PC-3 tumor growth in the bone of nude mice. The present data also showed that Pristimerin significantly inhibited VEGF-induced vasculogenesis of BM-EPCs by suppressing the EPCs functions including proliferation, adhesion, migration, tube formation and inactivation the phosphorylation of VEGFR-2, Akt and eNOS.
  
  
  CONCLUSIONS
  These data provide evidence that Pristimerin has strong potential for development as a novel agent against prostate bone metastasis by suppressing PC-3 stem cell characteristics and VEGF-induced vasculogenesis of BM-EPCs.
authors: Department of Orthopaedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors: Shuai
authors: S
authors: Huang
authors: Peiheng
authors: P
authors: He
authors: Xinsheng
authors: X
authors: Peng
authors: Jinglei
authors: J
authors: Li
authors: Dongliang
authors: D
authors: Xu
authors: Yubo
authors: Y
authors: Tang
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D010455:Peptides / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D053978:Pentacyclic Triterpenes; D010455:Peptides; C000606024:Prom1 protein, mouse; D014315:Triterpenes; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; C050414:celastrol