title: Anti-angiogenic potential of an ethanol extract of Annona atemoya seeds in vitro and in vivo.
abstract: BACKGROUND
  Angiogenesis, which is initiated by certain tumor micro-environmental conditions and diverse protein factors, plays a pivotal role during tumor development and metastasis. Therefore, many efforts have been made to develop effective anti-angiogenic agents as anticancer therapeutics. In the current study, we investigated the anti-angiogenic potential of an ethanol extract of Annona atemoya seeds (EEAA) in vitro and in vivo.
  
  
  METHODS
  The anti-angiogenic potential of EEAA was evaluated using various in vitro/in vivo models, including cell proliferation, migration, and tube formation by human umbilical vascular endothelial cells (HUVECs); a Matrigel plug assay; and tumor-induced angiogenesis. The expression of hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) was investigated using reverse transcription-polymerase chain reaction, immunoassays, and western blotting.
  
  
  RESULTS
  EEAA was able to significantly inhibit the angiogenic properties of HUVECs in vitro as well as angiogenic factor-induced blood vessel formation in vivo. EEAA down-regulated the expression of VEGF and HIF-1alpha/2alpha at the mRNA and protein levels, respectively, in cancer cells under hypoxic conditions.
  
  
  CONCLUSIONS
  EEAA shows a strong anti-angiogenic potential in both in vitro and in vivo systems, and we suggest that EEAA may be a valuable herbal source for anticancer drug development.
authors.forename: Jin-Mu
authors.initials: JM
authors.lastname: Yi
authors.forename: Jong-Shik
authors.initials: JS
authors.lastname: Park
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Ok-Sun
authors.initials: OS
authors.lastname: Bang
authors.affiliation: KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea. nosookim@kiom.re.kr.
authors.forename: No Soo
authors.initials: NS
authors.lastname: Kim
mesh_terms: D000704:Analysis of Variance; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D031041:Annona / Q000737:chemistry*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000431:Ethanol; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D051793:Hypoxia-Inducible Factor 1; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D000431:Ethanol