Cloning, sequencing, expression, and single-step purification of the adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase (CobU) from Salmonella typhimurium ATCC 19585

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Title:	Cloning, sequencing, expression, and single-step purification of the adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase (CobU) from Salmonella typhimurium ATCC 19585
Authors:	Hsu, FC;Ho, TJ;Lai, CC;Lin, CF;Chen, HP
Contributors:	中醫學院中醫所;Natl Taipei Univ Technol, Inst Biotechnol, Taipei 106, Taiwan;Natl Taipei Univ Technol, Dept Chem Engn, Taipei 106, Taiwan;China Med Univ, Grad Inst Chinese Med Sci, Taichung 404, Taiwan;China Med Univ, Sch Med, Taichung 404, Taiwan
Date:	2005
Issue Date:	2010-09-24 13:46:18 (UTC+8)
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Abstract:	Angiogenesis is a process that involves endothelial cell proliferation, migration, invasion, and tube formation, and inhibition of these processes has implications for angiogenesis- mediated disorders. The purpose of this study was to evaluate the antiangiogenic efficacy of YC- 1 [ 3-( 5'- hydroxymethyl- 2'- furyl)- 1-benzyl indazole] in well characterized in vitro and in vivo systems. YC- 1 inhibited the ability of vascular endothelial growth factor ( VEGF) and basic fibroblast growth factor ( bFGF) in a dose- dependent manner to induce proliferation, migration, and tube formation in human umbilical vascular endothelial cells; these outcomes were evaluated using [ H-3] thymidine incorporation, transwell chamber, and Matrigel- coated slide assays, respectively. YC- 1 inhibited VEGF- and bFGF- induced p42/ p44 mitogen- activated protein kinase and Akt phosphorylation as well as protein kinase C alpha translocation using Western blot analysis. The effect of YC- 1 on angiogenesis in vivo was evaluated using the mouse Matrigel implant model. YC- 1 administered orally in doses of 1 to 100 mg/ kg/ day inhibited VEGF- and bFGF- induced neovascularization in a dose- dependent manner over 7 days. These results indicate that YC- 1 has antiangiogenic activity at very low doses. Moreover, in transplantable murine tumor models, YC- 1 administered orally displayed a high degree of antitumor activity ( treatment- to- control life span ratio > 175%) without cytotoxicity. YC- 1 may be useful for treating angiogenesis- dependent human diseases such as cancer.
Relation:	PROTEIN EXPRESSION AND PURIFICATION 42(1):178-181
Appears in Collections:	[Graduate Institute of Chinese Medical Science] Journal articles

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