title: Deltonin inhibits angiogenesis by regulating VEGFR2 and subsequent signaling pathways in endothelial cells.
abstract: Deltonin is a steroidal saponin which could suppress tumor growth through suppressing angiogenesis, but the mechanisms have not been directly elucidated yet. In the present study, we showed that deltonin inhibited the proliferation of primary cultured human umbilical vein endothelial cells (HUVECs) in vitro; notably, it could significantly inhibit HUVECs migration, invasion, and tube formation, which are indispensable progresses of angiogenesis. We further demonstrated that deltonin could inhibit VEGF-induced blood vessel formation in vivo. What is more, we found that deltonin blocked VEGF triggered phosphorylation of key intracellular angiogenic molecules, such as VEGFR2, Src family kinase, focal adhesion kinase (FAK), extracellular signal-related kinase (Erk1/2) and AKT kinase, accompanied with the increase of phosphorylated P38MAPK. Taken together, the present study demonstrates that deltonin inhibits angiogenesis through regulating VEGFR2 signaling pathway as well as AKT/MAPK signaling pathways in endothelial cells.
authors.affiliation: Regenerative Medicine Research Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Regenerative Medicine Research Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Qingbing
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qing
authors.affiliation: Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Regenerative Medicine Research Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: wuxh@scu.edu.cn.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013150:Spirostans / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D013150:Spirostans; C016347:deltonin; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT/MAPK; Antiangiogenesis; Deltonin; HUVECs; VEGFR2