4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid inhibits angiogenesis via modulation of vascular endothelial growth factor receptor 2 signaling pathway

Tianli Zhou; Yunda Li; Heqiang Zhang; Lei Pan; Jinglong Pang; Qian Yuan; Guiyang Li; Lingjun Jie; Yan Wang; Yanhui Zhang

doi:10.3389/fcvm.2022.969616

4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid inhibits angiogenesis via modulation of vascular endothelial growth factor receptor 2 signaling pathway

Front Cardiovasc Med. 2022 Sep 23:9:969616. doi: 10.3389/fcvm.2022.969616. eCollection 2022.

Authors

Tianli Zhou¹, Yunda Li¹, Heqiang Zhang¹, Lei Pan¹, Jinglong Pang¹, Qian Yuan¹, Guiyang Li², Lingjun Jie^{1

2}, Yan Wang², Yanhui Zhang¹

Affiliations

¹ Institute of Cardiovascular Diseases, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
² Department of Cardiology, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Abstract

4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid (DCPIB), was discovered to be a potent and specific antagonist of volume-regulated anion channel that is closely linked to angiogenesis. However, the effect of DCPIB on angiogenesis remains unclear. Here, we found that DCPIB inhibited angiogenesis in the corneal suture and myocardial infarction in vivo model. In addition, DCPIB inhibited human umbilical vein endothelial cell migration, tube formation and proliferation in vitro. Moreover, DCPIB repressed the activation and expression of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling pathway. Computer modeling further confirmed that DCPIB binds with high affinity to VEGFR2. Collectively, we present evidence supporting an antiangiogenic role of DCPIB by targeting VEGFR2 signaling pathway, which suggests that DCPIB is a valuable lead compound for the treatment of angiogenesis-related diseases.

Keywords: 4-(2-Butyl-6; 7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid angiogenesis; angiogenesis; endothelial cell; vascular endothelial growth factor receptor 2; volume-regulated anion channel.