Broussonin A- and B-mediated inhibition of angiogenesis by blockade of VEGFR-2 signalling pathways and integrin beta 1 expression
- Authors
- Kim, Jae Hyeon; Kim, Sunho; Han, Surim; Ahn, Eun-Kyung; Cho, Young-Rak; Jeong, Wonsik; Kim, Sung Joon; Bae, Gyu-Un; Oh, Joa Sub; Seo, Dong-Wan
- Issue Date
- Feb-2022
- Publisher
- WILEY
- Keywords
- broussonin A; broussonin B; integrin beta 1; vascular endothelial growth factor
- Citation
- JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, v.26, no.4, pp 1194 - 1205
- Pages
- 12
- Journal Title
- JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
- Volume
- 26
- Number
- 4
- Start Page
- 1194
- End Page
- 1205
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/145929
- DOI
- 10.1111/jcmm.17173
- ISSN
- 1582-1838
1582-4934
- 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 beta 1 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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