Sanguiin H-6 blocks endothelial cell growth through inhibition of VEGF binding to VEGF receptor.
The vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, which is a process where new blood vessels develop from the endothelium of a pre-existing vasculature. VEGF exerts its activity by binding to its receptor tyrosine kinase, KDR/Flk-1, which is expressed on the surface of endothelial cells. A methanol extract and organic solvent (n-hexane, ethyl acetate, n-butanol, aqueous) fractions from Rubus coreanus were examined for their inhibitory effects on VEGF binding to the VEGF receptor. The methanol extract from the crude drug were found to significantly inhibit VEGF binding to the VEGF receptor (IC50 approximately = 27 microg/mL). Among the fractions examined, the aqueous fraction from the medicinal plant showed potent inhibitory effects against the binding of KDR/Flk-1-Fc to immobilized VEGF165 in a dose-dependent manner (IC50 approximately = 11 microg/mL). Sanguiin H-6 was isolated as an active principle from the aqueous fraction, and inhibited the binding of KDR/Flk-1-Fc to immobilized VEGF165 in a dose-dependent manner (IC50 approximately = 0.3 microg/mL). In addition, sanguiin H-6 efficiently blocked the VEGF-induced HUVEC proliferation in a dose-dependent manner (IC50 approximately = 7.4 microg/mL) but had no effect on the growth of HT1080 human fibrosarcoma cells. This suggests that sanguiin H-6 might be a potential anti-angiogenic agent.
Lee
Sung-Jin
SJ
Gyeonggi Regional Research Center, Hankyong National University, Ansung, Gyeonggi 456-749, Korea. genielee@dreamwiz.com
Lee
Hak-Kyo
HK
D002240:Carbohydrate Sequence; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D005638:Fruit / Q000737:chemistry; D006801:Humans; D047348:Hydrolyzable Tannins / Q000302:isolation & purification / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; C013515:ellagitannin; C081844:sanguiin H 6; D040262:Receptors, Vascular Endothelial Growth Factor