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KMID : 0620920190510100120
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Experimental & Molecular Medicine
2019 Volume.51 No. 10 p.120 ~ p.120
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6′-Sialylgalactose inhibits vascular endothelial growth factor receptor 2-mediated angiogenesis
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Chung Tae-Wook
Kim Eun-Yeong
Choi Hee-Jung
Han Chang-Woo
Jang Se-Bok
Kim Keuk-Jun
Jin Ling
Koh Young-Jun
Ha Ki-Tae
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Abstract
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Angiogenesis should be precisely regulated because disordered neovascularization is involved in the aggravation of multiple diseases. The vascular endothelial growth factor (VEGF)-A/VEGF receptor 2 (VEGFR-2) axis is crucial for controlling angiogenic responses in vascular endothelial cells (ECs). Therefore, inactivating VEGFR-2 signaling may effectively suppress aberrant angiogenesis and alleviate related symptoms. In this study, we performed virtual screening, identified the synthetic disaccharide 6′-sialylgalactose (6SG) as a potent VEGFR-2-binding compound and verified its high binding affinity by Biacore assay. 6SG effectively suppressed VEGF-A-induced VEGFR-2 phosphorylation and subsequent in vitro angiogenesis in HUVECs without inducing cytotoxicity. 6SG also inhibited VEGF-A-induced extracellular-regulated kinase (ERK)/Akt activation and actin stress fiber formation in HUVECs. We demonstrated that 6SG inhibited retinal angiogenesis in a mouse model of retinopathy of prematurity and tumor angiogenesis in a xenograft mouse model. Our results suggest a potential therapeutic benefit of 6SG in inhibiting angiogenesis in proangiogenic diseases, such as retinopathy and cancer.
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KEYWORD
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Drug development, Tumour angiogenesis
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