Compound K inhibits basic fibroblast growth factor-induced angiogenesis via regulation of p38 mitogen activated protein kinase and AKT in human umbilical vein endothelial cells.
Compound K (CK; 20-O-beta-D-glucopyranosyl-20(S)-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 (HUVECs). 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.
College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Arong
A
Jeong
Hyo-Jung
HJ
Lee
Soo-Jin
SJ
Jeong
Hyo-Jeong
HJ
Lee
Eun-Ok
EO
Lee
Hyunsu
H
Bae
Sung-Hoon
SH
Kim
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D003094:Collagen; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D016222:Fibroblast Growth Factor 2; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D007797:Laminin; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism; D005894:Panax / Q000737:chemistry; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011509:Proteoglycans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D003094:Collagen; D019938:Cyclin D1; D004338:Drug Combinations; D005136:Eye Proteins; D016222:Fibroblast Growth Factor 2; D036145:Ginsenosides; D007797:Laminin; D009414:Nerve Growth Factors; D010936:Plant Extracts; D011509:Proteoglycans; D051057:Proto-Oncogene Proteins c-akt; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D048051:p38 Mitogen-Activated Protein Kinases; D000099174:Pigment Epithelium-Derived Factor; C059485:matrigel; C112772:ginsenoside compound K