Open AccessBroussonin A– and B–mediated inhibition of angiogenesis by blockade of VEGFR‐2 signalling pathways and integrin β1 expression
Author(s) -
Kim Jae Hyeon,
Kim Sunho,
Han Surim,
Ahn EunKyung,
Cho YoungRak,
Jeong Wonsik,
Kim Sung Joon,
Bae GyuUn,
Oh Joa Sub,
Seo DongWan
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17173
Subject(s) - angiogenesis , integrin , microbiology and biotechnology , endothelial stem cell , cancer research , biology , cell growth , vascular endothelial growth factor , vascular endothelial growth factor a , neovascularization , cell , chemistry , in vitro , vegf receptors , biochemistry
In the present study, we demonstrate the regulatory effects and mechanism of broussonin A and B, diphenylpropane derivatives isolated from Broussonetia kazinoki , on vascular endothelial growth factor‐A (VEGF‐A)–stimulated endothelial cell responses in vitro and microvessel sprouting ex vivo. Treatment with broussonin A or B suppressed VEGF‐A‐stimulated endothelial cell proliferation by regulating the expression of cell cycle–related proteins and the phosphorylation status of retinoblastoma protein. In addition, treatment with broussonin A or B abrogated VEGF‐A‐stimulated angiogenic responses including endothelial cell migration, invasion, tube formation and microvessel formation from rat aortic rings. These anti‐angiogenic activities of broussonin A and B were mediated through inactivation of VEGF‐A‐stimulated downstream signalling pathways, localization of vascular endothelial‐cadherin at cell‐cell contacts, and down‐regulation of integrin β1 and integrin‐liked kinase. Furthermore, treatment with broussonin A or B inhibited proliferation and invasion of non–small cell lung cancer and ovarian cancer cells. Taken together, our findings suggest the pharmacological potential of broussonin A and B in the regulation of angiogenesis, cancer cell growth and progression.