期刊
CANCER LETTERS
卷 369, 期 2, 页码 323-330出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.09.021
关键词
Marmesin; Angiogenesis inhibitor; Vascular endothelial growth factor; VEGFR-2; beta 1 integrin
类别
资金
- R&D Program for Forestry Technology through the Korea Forest Service [S121313L070100]
- Basic Science Research Program through the National Research Foundation of Korea, Ministry of Education [2010-0021913, 2014R1A1A2058015]
- National Research Foundation of Korea [2014R1A1A2058015, 2010-0021913] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
In the present study, we investigated the effects and molecular mechanism of marmesin, a coumarin compound isolated from Broussonetia kazinoki, on vascular endothelial growth factor-A (VEGF-A)-induced endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. Marmesin treatment inhibited VEGF-A-stimulated endothelial cell proliferation through down-regulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. In addition, marmesin treatment abrogated VEGF-A-induced endothelial cell migration, invasion and capillary-like structure formation in vitro as well as angiogenic sprouting ex vivo. These anti-angiogenic activities of marmesin were mediated through inactivation of VEGF-A-stimulated signaling pathways, and down-regulation of cell surface signaling molecules including VEGF receptor-2, human epidermal growth factor receptor-2, integrin beta 1 and integrin-liked kinase. Taken together, these findings clearly support the pharmacological roles of marmesin in regulating angiogenesis, and warrant further evaluation and development as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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