1,2,3,4,6-Penta-O-galloyl-beta-D-glucose blocks endothelial cell growth and tube formation through inhibition of VEGF binding to VEGF receptor.
Tumor angiogenesis is a critical step for the growth and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) is the most important angiogenic molecule associated with tumor-induced neovascularization. VEGF exerts its activity through binding to its receptor tyrosine kinase, KDR/Flk-1, expressed on the surface of endothelial cells. From the screening of medicinal plants, we have identified 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG) from the roots of Paeonia lactiflora that inhibited the binding of VEGF to KDR/Flk-1. PGG efficiently blocked VEGF-induced human umbilical vein endothelial cell proliferation and the growth of immortalized human microvascular endothelial cells, but did not affect the growth of HT1080 human fibrosarcoma and DU-145 human prostate carcinoma cells. PGG also blocked VEGF-induced capillary-like tube formation of endothelial cell on Matrigel. Our results suggest that PGG could be a candidate for developing anti-angiogenic agent.
Lee
Sung-Jin
SJ
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 110-460, South Korea.
Lee
Hwan Myung
HM
Ji
Seung-Taek
ST
Lee
Seung-Rock
SR
Mar
Woongchon
W
Gho
Yong Song
YS
D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047348:Hydrolyzable Tannins; D007797:Laminin / Q000737:chemistry; D008297:Male; D029596:Paeonia / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects*; D011509:Proteoglycans / Q000737:chemistry; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013634:Tannins / Q000494:pharmacology*; D014471:Umbilical Veins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D004338:Drug Combinations; D047348:Hydrolyzable Tannins; D007797:Laminin; D010936:Plant Extracts; D011509:Proteoglycans; D013634:Tannins; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; C435084:pentagalloylglucose; D003094:Collagen; D040262:Receptors, Vascular Endothelial Growth Factor; D000254:Sodium-Potassium-Exchanging ATPase