Abstract
Compound K (CK; 20-0-β-D-glucopyranosyl-20(5)-protopanaxadiol), an active ginseng saponin metabolite, exerts anticancer activity via apoptosis induction in various cancers. In the present study, we investigated the anti-angiogenic activity of CK and its molecular mechanisms in human umbilical vein endothelial cells (HU-VECs). Angiogenesis was induced in HUVECS by basic fibroblast growth factor (bFGF), a potent angiogenic growth factor. CK significantly inhibited the proliferation and also attenuated the expression of a proliferating protein cyclin D1 in bFGF treated HUVECs. Also, CK significantly inhibited the migration and tube formation of bFGF treated HUVECs at non-cytotoxic concentrations, reduced secreted level of vascular endothelial growth factor (VEGF) and increased the secreted level of pigment epithelium-derived factor (PEDF) in HUVECs. In addition, CK effectively disrupted bFGF-induced neo-vascularization in the Matrigel plugs excised from mice in vivo. Notably, we have found that CK downregulated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and AKT in bFGF treated HUVECs. Taken together, our findings for the first time indicate that CK exerts anti-angiogenic activity via inhibition of p38 MAPK and AKT in HUVECs with the potential of a cancer chemopreventive agent. © 2010 Pharmaceutical Society of Japan.
Author keywords
AKT; Angiogenesis; Compound K; Human umbilical vein endothelial cell; p38 mitogen-activated protein kinase
Indexed keywords
EMTREE drug terms: 20 o beta dextro glucopyranosyl 20 protopanaxadiol; antineoplastic agent; basic fibroblast growth factor; cyclin D1; mitogen activated protein kinase p38; pigment epithelium derived factor; protein kinase B; saponin derivative; unclassified drug; vasculotropin
EMTREE medical terms: animal cell; animal experiment; article; cell migration; cell proliferation; concentration response; controlled study; down regulation; drug mechanism; endothelium cell; enzyme inhibition; enzyme phosphorylation; enzyme regulation; human; human cell; mouse; nonhuman; protein expression; protein secretion; umbilical vein
MeSH: Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Phytogenic; Cell Proliferation; Collagen; Cyclin D1; Down-Regulation; Drug Combinations; Endothelial Cells; Endothelium, Vascular; Eye Proteins; Fibroblast Growth Factor 2; Ginsenosides; Humans; Laminin; Mice; Mice, Inbred C57BL; Nerve Growth Factors; p38 Mitogen-Activated Protein Kinases; Panax; Phosphorylation; Plant Extracts; Proteoglycans; Proto-Oncogene Proteins c-akt; Serpins; Umbilical Veins; Vascular Endothelial Growth Factor A
Medline is the source for the MeSH terms of this document.
Chemicals and CAS Registry Numbers: basic fibroblast growth factor, 106096-93-9; pigment epithelium derived factor, 197980-93-1; protein kinase B, 148640-14-6; vasculotropin, 127464-60-2;Angiogenesis Inhibitors; Antineoplastic Agents, Phytogenic; Collagen, 9007-34-5; Cyclin D1, 136601-57-5; Drug Combinations; Eye Proteins; Fibroblast Growth Factor 2, 103107-01-3; Ginsenosides; Laminin; Nerve Growth Factors; Plant Extracts; Proteoglycans; Proto-Oncogene Proteins c-akt, 2.7.11.1; Serpins; Vascular Endothelial Growth Factor A; ginsenoside M1; matrigel, 119978-18-6; p38 Mitogen-Activated Protein Kinases, 2.7.11.24; pigment epithelium-derived factor