Abstract

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.

Details

Title
6′-Sialylgalactose inhibits vascular endothelial growth factor receptor 2-mediated angiogenesis
Author
Tae-Wook Chung 1 ; Eun-Yeong, Kim 1 ; Hee-Jung, Choi 1 ; Chang Woo Han 2 ; Jang, Se Bok 2 ; Keuk-Jun Kim 3 ; Ling, Jin 1 ; Young Jun Koh 4 ; Ki-Tae Ha 1   VIAFID ORCID Logo 

 Department of Korean Medical Science, School of Korean Medicine and Healthy Aging Korean Medical Research Center, Pusan National University, Yangsan, Gyeongnam, Korea 
 Department of Molecular Biology, College of Natural Sciences, Pusan National University, Geumjeong-gu, Busan, Korea 
 Department of Clinical Pathology, TaeKyeung University, Gyeongsan, Gyeongbuk, Korea 
 Department of Pathology, College of Korean Medicine, Dongguk University, Goyang, Gyeonggi-do, Korea; GI Innovation, Inc., A-1116, Tera Tower, Songpa-daero 167, Songpa-gu, Seoul, Korea 
Pages
1-13
Publication year
2019
Publication date
Oct 2019
Publisher
Springer Nature B.V.
ISSN
12263613
e-ISSN
20926413
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2304114385
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.