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KMID : 0578320180410080771
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Molecules and Cells
2018 Volume.41 No. 8 p.771 ~ p.780
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Oleanolic Acids Inhibit Vascular Endothelial Growth Factor Receptor 2 Signaling in Endothelial Cells: Implication for Anti-Angiogenic Therapy
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Lee Da-Hye
Lee Jung-Sul
Jeon Jong-Wook
Kim Kyung-Jin
Yun Jang-Hyuk
Jeong Han-Seok
Lee Eun-Hui
Koh Young-Jun
Cho Chung-Hyun
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Abstract
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Angiogenesis must be precisely controlled because uncontrolled angiogenesis is involved in aggravation of disease symptoms. Vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR-2) signaling is a key pathway leading to angiogenic responses in vascular endothelial cells (ECs). Therefore, targeting VEGF/VEGFR-2 signaling may be effective at modulating angiogenesis to alleviate various disease symptoms. Oleanolic acid was verified as a VEGFR-2 binding chemical from anticancer herbs with similar binding affinity as a reference drug in the Protein Data Bank (PDB) entry 3CJG of model A coordination. Oleanolic acid effectively inhibited VEGF-induced VEGFR-2 activation and angiogenesis in HU-VECs without cytotoxicity. We also verified that oleanolic acid inhibits in vivo angiogenesis during the development and the course of the retinopathy of prematurity (ROP) model in the mouse retina. Taken together, our results suggest a potential therapeutic benefit of oleanolic acid for inhibiting angiogenesis in proangiogenic diseases, including retinopathy.
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KEYWORD
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angiogenesis, endothelial cells, oleanolic acid, retinopathy of prematurity, VEGFR-2
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