title: Indirubin derivative E804 inhibits angiogenesis.
abstract: BACKGROUND
  It has previously been shown that indirubin derivative E804 (IDR-E804) blocks signal transducer and activator of transcription-3 signaling in human breast and prostate cancer cells and inhibits Src kinase activity. To further establish its role in angiogenesis, we tested its potential using human umbilical vein endothelial cells (HUVECs) and analyzed the effects of IDR-E804 on cellular and molecular events related to angiogenesis.
  
  
  METHODS
  The anti-angiogenic effects of IDR-E804 were examined by assessing the proliferation, migration and capillary tube formation of HUVECs were induced by vascular endothelial growth factor (VEGF) with or without various concentrations of IDR-E804. The inhibitory effect of IDR-E804 angiogenesis and tumor growth in vivo was also investigated in Balb/c mice subcutaneously transplanted with CT-26 colon cancer cells.
  
  
  RESULTS
  IDR-E804 significantly decreased proliferation, migration and tube formation of vascular endothelial growth factor VEGF-treated HUVECs. These effects were accompanied by decreased phosphorylation of VEGF receptor (VEGFR)-2, AKT and extracellular signal regulated kinase in VEGF-treated HUVECs. Intratumor injections of IDR-E804 inhibited the growth of subcutaneously inoculated CT-26 allografts in syngenic mice. Immunohistochemistry revealed a decreased CD31 microvessel density index and Ki-67 proliferative index, but an increased apoptosis index in IDR-E804-treated tumors.
  
  
  CONCLUSIONS
  These data revealed that IDR-E804 is an inhibitor of angiogenesis and also provide evidence for the efficacy of IDR-E804 for anti-tumor therapies.
authors.affiliation: Center for Efficacy Assessment and Development of Functional Foods andDrugs, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Shin
authors.forename: Jin-Kyung
authors.initials: JK
authors.lastname: Kim
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D055806:Microvessels / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010091:Oximes; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; C509867:Indirubin E804; D007211:Indoles; D010091:Oximes; D040301:Vascular Endothelial Growth Factor Receptor-2; C027185:indirubin