title: Anti-angiogenic activity of salvicine.
abstract: BACKGROUND
  Salvicine is a pharmacologically active derivative from Chinese medicinal plant Salvia prionitis Hance (Labiatae). It has been reported that salvicine inactivates β1 integrin and inhibits integrin-mediated cell adhesion to fibronectin. Given the emerging correlation between integrins and angiogenesis, we propose that salvicine abolishes cell adhesion and subsequent metastasis by inhibiting angiogenisis.
  
  
  OBJECTIVE
  The anti-angiogenesis activities of salvicine were investigated for the first time.
  
  
  METHODS
  The cytotoxicity of salvicine on human microvascular endothelial cells (HMECs) and non-small cell lung adenocarcinoma A549 cells were measured at doses between 0.625 and 200 µM. Changes of cell migration were detected with doses of salvicine at 1.25-5 µM, and basement membrane matrigel matrix was used for the assessment of tube formation at concentrations ranging from 0.078 to 1.25 µM. In addition, mRNA expression of basic fibroblast growth factor (bFGF) in A549 cells was studied with the RT-PCR assay.
  
  
  RESULTS
  In vitro studies revealed that the IC50 of salvicine on A549 cells (18.66 µM) was two-fold higher than that of HMECs (7.91 µM). Salvicine (1.25, 2.5 and 5.0 μM) inhibited significantly the endothelial cell migration up to 56, 73 and 82%, respectively. Salvicine decreased capillary-like tube formation of HMECs with high potency. Furthermore, it (30 µM) markedly reduced the mRNA expression of bFGF in A549 cells, while vascular endothelial growth factor (VEGF) mRNA expression remained unchanged.
  
  
  CONCLUSIONS
  Our results suggest that salvicine has potent anti-angiogenic activity through the inhibition on the sequential angiogenic cascades: proliferation, migration and tube formation and is associated with influence on the expression of bFGF of tumor cell.
authors.affiliation: Yunnan Key Laboratory of Pharmacology for Natural Products, School of Pharmaceutical Science, Kunming Medical University, Kunming, PR China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Chen
authors.initials: C
authors.lastname: Qing
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D009285:Naphthoquinones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027544:Salvia / Q000737:chemistry*
chemical_list: D020533:Angiogenesis Inhibitors; D004365:Drugs, Chinese Herbal; D009285:Naphthoquinones; D012333:RNA, Messenger; C122096:salvicine; D016222:Fibroblast Growth Factor 2