title: Marmesin is a novel angiogenesis inhibitor: Regulatory effect and molecular mechanism on endothelial cell fate and angiogenesis.
abstract: 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 β1 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.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea.
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Gyeonggi Biocenter, Gyeonggi Institute of Science & Technology Promotion, Suwon 16229, Republic of Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Gyeonggi Biocenter, Gyeonggi Institute of Science & Technology Promotion, Suwon 16229, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Ahn
authors.affiliation: Gyeonggi Biocenter, Gyeonggi Institute of Science & Technology Promotion, Suwon 16229, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Ko
authors.affiliation: Gyeonggi Biocenter, Gyeonggi Institute of Science & Technology Promotion, Suwon 16229, Republic of Korea.
authors.forename: Young-Rak
authors.initials: YR
authors.lastname: Cho
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea.
authors.forename: Choong Hyun
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 04310, Republic of Korea.
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 04310, Republic of Korea.
authors.forename: Gyu-Un
authors.initials: GU
authors.lastname: Bae
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea; Gyeonggi Biocenter, Gyeonggi Institute of Science & Technology Promotion, Suwon 16229, Republic of Korea. Electronic address: jsoh@dankook.ac.kr.
authors.forename: Joa Sub
authors.initials: JS
authors.lastname: Oh
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea. Electronic address: dwseomb@dankook.ac.kr.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Seo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D003374:Coumarins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics*; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D003374:Coumarins; D040301:Vascular Endothelial Growth Factor Receptor-2; C001684:marmesin
keywords: Angiogenesis inhibitor; Marmesin; VEGFR-2; Vascular endothelial growth factor; β1 integrin