title: In vitro screening for angiostatic potential of herbal chemicals.
abstract: OBJECTIVE
  Herbal medicine has long been used in traditional medicinal systems. The authors carried out a first-line screening of four herbal chemicals with reported antioxidative properties and capabilities to suppress endothelial cell growth and migration. These herbal chemicals were isoliquiritigenin (ISL) from licorice, epigallocatechin gallate (EGCG) from green tea, resveratrol (Rst) from grapes, and gambogic acid (GA) from the resin of Garcinia hanburyi.
  
  
  METHODS
  Cytotoxicity was studied by MTT cell viability/proliferation assay on human retinal pigment epithelial cells (ARPE19). Effects on vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation and migration were investigated by a scratch-wound model using human umbilical vein endothelial cells (HUVECs). The effects on VEGF signaling in HUVECs were analyzed by Western blotting.
  
  
  RESULTS
  At sub-cytotoxic levels, ISL (10 μM), EGCG (50 μM), and Rst (10 μM) suppressed HUVEC proliferation and migration under VEGF (20 ng/mL) stimulation in our scratch-wound model. HUVEC migration was reduced more by ISL and EGCG than bevacizumab, a humanized monoclonal antibody against VEGF. The efficiency of Rst was similar to that of bevacizumab. GA, however, was toxic to cells even at nanomolar concentrations. Western blot analysis showed that these chemicals affected focal adhesion kinase activation and expression of pigment epithelial growth factor.
  
  
  CONCLUSIONS
  ISL, EGCG, and Rst are highly effective and efficient in suppressing endothelial cell proliferation and migration, with low cytotoxicity on ARPE19 and HUVEC lines. They are potentially useful for further investigation to develop antiangiogenic therapies by virtue of their small molecular sizes for easy penetration through tissue cells and their low effective dosages.
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Liming
authors.initials: L
authors.lastname: Cao
authors.forename: Huanming
authors.initials: H
authors.lastname: Liu
authors.forename: Dennis Shun-Chiu
authors.initials: DS
authors.lastname: Lam
authors.forename: Gary Hin-Fai
authors.initials: GH
authors.lastname: Yam
authors.forename: Chi-Pui
authors.initials: CP
authors.lastname: Pang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism; D028321:Plant Preparations / Q000494:pharmacology*; D000077185:Resveratrol; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects; D015843:Serpins / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D044004:Xanthones / Q000633:toxicity; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002392:Catechin; D047188:Chalcones; D005136:Eye Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D009414:Nerve Growth Factors; D028321:Plant Preparations; D000077185:Resveratrol; D015843:Serpins; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D044004:Xanthones; D000099174:Pigment Epithelium-Derived Factor; C052659:gambogic acid; C040920:isoliquiritigenin; C045651:epigallocatechin gallate