title: Broussonetia kazinoki modulates the expression of VEGFR-2 and MMP-2 through the inhibition of ERK, Akt and p70S6K‑dependent signaling pathways: Its implication in endothelial cell proliferation, migration and tubular formation.
abstract: Broussonetia kazinoki (BK) has been used as a traditional medicine to improve vision, as well as for inflammatory and infectious diseases. In the present study, we investigated the effects and molecular mechanism of the ethanolic extract of BK on cell proliferation, migration and tubular formation in vascular endothelial growth factor-A (VEGF-A)-treated human umbilical vein endothelial cells. BK treatment inhibited VEGF-A-stimulated endothelial cell proliferation through the downregulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins. Moreover, BK treatment suppressed cell migration and tubular formation in response to VEGF-A. These anti-angiogenic activities of BK were associated with the inactivation of mitogenic signaling pathways including extracellular signal-regulated kinase, Akt and p70S6K, and the subsequent downregulation of VEGFR-2 and matrix metalloproteinase-2. Taken together, these findings suggest further evaluation and development of BK as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Young-Rak
authors.initials: YR
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Natural Products Research Institute, Gyeonggi Institute of Science and Technology Promotion, Suwon 443-270, Republic of Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Natural Products Research Institute, Gyeonggi Institute of Science and Technology Promotion, Suwon 443-270, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Ahn
authors.affiliation: Natural Products Research Institute, Gyeonggi Institute of Science and Technology Promotion, Suwon 443-270, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Ko
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: In
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Gyu-Un
authors.initials: GU
authors.lastname: Bae
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Joa Sub
authors.initials: JS
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Seo
mesh_terms: D031623:Broussonetia; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D010936:Plant Extracts; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2