title: Betaine inhibits in vitro and in vivo angiogenesis through suppression             of the NF-κB and Akt signaling pathways.
abstract: Angiogenesis is defined as the formation of new blood vessels form existing             vessels surrounding a tumor. The process of angiogenesis is an important step             for tumor growth and metastasis, as is inflammation. Thus, angiogenesis inhibitors             that suppress inflammation have been studied as an anticancer treatment. Recently,             many research groups have investigated the anti-angiogenic activity of natural             compounds since some have been demonstrated to have anticancer properties. Among             many natural compounds, we focused on betaine, which is known to suppress inflammation.             Betaine, trimethylglycine (TMG), was first discovered in the juice of sugar beets             and was later shown to be present in wheat, shellfish and spinach. In Southeast             Asia, betaine is used in traditional oriental medicine for the treatment of hepatic             disorders. Here, we report the anti-angiogenic action of betaine. Betaine inhibited             in vitro angiogenic cascade, tube formation, migration and invasion of human umbilical             vein endothelial cells (HUVECs). Betaine also inhibited in vivo angiogenesis in             the mouse Matrigel plug assay. The mRNA expression levels of basic fibroblast             growth factor (bFGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9             (MMP-9) in HUVECs were decreased by betaine treatment. In addition, betaine suppressed             NF-κB and Akt activation.
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan                     609-735, Republic of Korea.
authors.forename: Eui-Yeun
authors.initials: EY
authors.lastname: Yi
authors.forename: Yung-Jin
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001622:Betaine / Q000008:administration & dosage / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D016328:NF-kappa B; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D001622:Betaine; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9