Naringenin exerts anti-angiogenic effects in human endothelial cells: Involvement of ERRα/VEGF/KDR signaling pathway.
Naringenin (Nar), most abundant in oranges and tomatoes, are known for the hypocholesterolemic, anti-estrogenic, hypolipidemic, anti-hypertensive, and anti-inflammatory activities. Here, the present study was designed to investigate the in vitro and in vivo anti-angiogenesis of Nar. Inhibition of angiogenesis was determined in vitro by using proliferation, apoptosis, migration, and tube-formation assays in Nar-treated human endothelial cell. Finally, CAM assays were used to assess inhibitory effect of Nar on physiological angiogenesis in vivo. The data suggest that Nar should be a direct ERRα inhibitor capable of inhibiting angiogenesis in vitro and in vivo, including endothelial cell proliferation, survival, migration and capillary-like structures formation of HUVECs, as well as reduced neovascularization of the CAM. Furthermore, the effects exerted by Nar are cell cycle related and mediated by VEGF/KDR signaling pathway along with downregulation of certain proangiogenic inflammatory cytokines. Our data thus provide potential molecular mechanisms through which Nar manifests it as a promising anti-angiogenic and anti-cancer agent.
Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, Shanghai 200040, China; Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, Shanghai 201907, China. Electronic address: qyli1234@163.com.
Qunyi
Q
Li
Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, Shanghai 201907, China.
Yi
Y
Wang
Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, Shanghai 201907, China.
Liudi
L
Zhang
Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, Shanghai 201907, China.
Lu
L
Chen
School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, Jinan 250353, China.
Yongli
Y
Du
General Surgery Unit, Huashan Hospital, Fudan University, 12 Wu Lu Mu Qi M Road, Shanghai 200040, China. Electronic address: Yeting_0525@hotmail.com.
Ting
T
Ye
Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, Shanghai 200040, China; Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, Shanghai 201907, China.
Xiaojin
X
Shi
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D044950:Flavanones / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D000097983:ERRalpha Estrogen-Related Receptor
D020533:Angiogenesis Inhibitors; D044950:Flavanones; D011960:Receptors, Estrogen; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000097983:ERRalpha Estrogen-Related Receptor; C467484:VEGFA protein, human; C000588866:KDR protein, human; C005273:naringenin
Angiogenesis; Endothelial cells; Estrogen related receptor α; Migration; Naringenin; Naringenin (PubChem CID: 932); Proliferation; Tube formation; Vascular endothelial growth factor-A