title: Syzygium campanulatum korth methanolic extract inhibits angiogenesis and tumor growth in nude mice.
abstract: BACKGROUND
  Syzygium campanulatum Korth (Myrtaceae) is an evergreen shrub rich in phenolics, flavonoid antioxidants, and betulinic acid. This study sought to investigate antiangiogenic and anti-colon cancer effects of S.C. standardized methanolic extract.
  
  
  METHODS
  Betulinic acid was isolated from methanolic extract by crystallization and chromatography techniques. S.C. methanolic extract was analyzed by UV-Vis spectrophotometry, FTIR, LC-MS, and HPLC. Antiangiogenic effect was studied on rat aortic rings, matrigel tube formation, cell proliferation and migration, and expression of vascular endothelial growth factor (VEGF). Antitumor effect was studied using a subcutaneous tumor model of HCT 116 colorectal carcinoma cells established in nude mice.
  
  
  RESULTS
  Analysis by HPLC, LC-MS and FTIR confirm presence of betulinic acid in S.C. methanolic extract. Quantitative analysis by HPLC indicates presence of betulinic acid in S.C. extract at 5.42 ± 0.09% (w/w). Antiangiogenesis study showed potent inhibition of microvessels outgrowth in rat aortic rings, and studies on normal and cancer cells did not show any significant cytotoxic effect. Antiangiogenic effect was further confirmed by inhibition of tube formation on matrigel matrix that involves human endothelial cells (IC50 = 17.6 ± 2.9 μg/ml). S.C. extract also inhibited migration of endothelial cells and suppressed expression of VEGF. In vivo antiangiogenic study showed inhibition of new blood vessels in chicken embryo chorioallantoic membrane (CAM), and in vivo antitumor study showed significant inhibition of tumor growth due to reduction of intratumor blood vessels and induction of cell death.
  
  
  CONCLUSIONS
  Collectively, our results indicate S. campanulatum as antiangiogenic and antitumor candidate, and a new source of betulinic acid.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Pulau Pinang, Malaysia. abedaisheh@yahoo.com
authors.forename: Abdalrahim F A
authors.initials: AF
authors.lastname: Aisha
authors.forename: Zhari
authors.initials: Z
authors.lastname: Ismail
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Abu-Salah
authors.forename: Jamshed M
authors.initials: JM
authors.lastname: Siddiqui
authors.forename: Gheniya
authors.initials: G
authors.lastname: Ghafar
authors.forename: Amin Malik Shah
authors.initials: AM
authors.lastname: Abdul Majid
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D027842:Syzygium / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D006131:Growth Inhibitors; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A