Chrysin suppresses IL-6-induced angiogenesis via down-regulation of JAK1/STAT3 and VEGF: an in vitro and in ovo approach.
Chrysin, 5,7-dihydroxyflavone, possesses many biologic properties. This study aimed to investigate the effects and molecular mechanisms of chrysin on IL-6-induced angiogenesis in vitro and in ovo. Chicken chorioallantoic membrane assay, an in ovo angiogenesis assay, showed chrysin significantly suppressed IL-6-induced neovascularization. Furthermore, chrysin significantly suppressed human umbilical vein endothelial cell (HUVECs) migration and tube formation. The signaling pathway involved in chrysin-related antiangiogenesis was also investigated. The data indicated that chrysin is able to down-regulate the expression of glycoprotein 130 (gp130), soluble IL-6 receptor (IL-6R), phosphorylated JAK1 and STAT3, and VEGF in HUVECs. The IL-6-induced binding of STAT3 was significantly suppressed by chrysin. Moreover, chrysin did not further suppress VEGF expression with STAT3 knocked down. Taken together, the results show that chrysin suppresses IL-6-induced angiogenesis through modulation of the sIL-6R/gp130/JAK1/STAT3/VEGF signaling pathway. Chrysin may provide new therapeutic potential for IL-6-induced pathological angiogenesis.
Lin
Chiu-Mei
CM
Department of Emergency Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei City, Taiwan.
Shyu
Kou-Gi
KG
Wang
Bao-Wei
BW
Chang
Hang
H
Chen
Yen-Hsu
YH
Chiu
Jen-Hwey
JH
D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000494:pharmacology*; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D005419:Flavonoids; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; C043561:chrysin; D053613:Janus Kinase 1