Wogonin inhibits IL-6-induced angiogenesis via down-regulation of VEGF and VEGFR-1, not VEGFR-2.
So far, no antiangiogenic activity of wogonin, a flavonoid, on human umbilical vein endothelial cells (HUVECs) has been demonstrated. The aim of this study was to investigate the effects of wogonin on IL-6-induced angiogenesis in HUVEC cultures and chorioallantoic membrane (CAM) neovascularization. The in vivo CAM model was applied to evaluate the percentage of new vessel formations, followed by measurement of endothelial migration and tube formation in HUVEC cultures. The results revealed that wogonin (10(-8) approximately 10(-5)M) concentration-dependently inhibited IL-6-induced angiogenesis. The signaling pathway was through down-regulation of the autocrine loop of VEGF and VEGFR-1, but not of VEGFR-2. Furthermore, the regulating loop of the IL-6 receptor complex was also attenuated via expression of sIL-6Ralpha and gp130, but not of IL-6/IL-6R binding density. We conclude that wogonin is a suppressive agent of the autoregulated loop of VEGF, VEGFR-1 and the IL-6 receptor complex.
Lin
Chiu-Mei
CM
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Chang
Hang
H
Chen
Yeh-Hsu
YH
Wu
I-Hsing
IH
Chiu
Jen-Hwey
JH
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000166:cytology; D044950:Flavanones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015850:Interleukin-6; D008517:Phytotherapy; D010946:Plants, Medicinal; D040262:Receptors, Vascular Endothelial Growth Factor / Q000187:drug effects*; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects*
D020533:Angiogenesis Inhibitors; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; C085514:wogonin