Broussonin A– and B–mediated inhibition of angiogenesis by blockade of VEGFR‐2 signalling pathways and integrin β1 expression |
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Authors: | Jae Hyeon Kim,Sunho Kim,Surim Han,Eun‐ Kyung Ahn,Young‐ Rak Cho,Wonsik Jeong,Sung Joon Kim,Gyu‐ Un Bae,Joa Sub Oh,Dong‐ Wan Seo |
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Affiliation: | 1. Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan Republic of Korea ; 2. Biocenter, Gyeonggi Business & Science Accelerator, Suwon Republic of Korea ; 3. Department of Pharmacy, College of Pharmacy, Sookmyung Women’s University, Seoul Republic of Korea |
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Abstract: | 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. |
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Keywords: | broussonin A, broussonin B, integrin β 1, vascular endothelial growth factor |
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