title: Antitumor and anti-angiogenic activity of the recombinant human disintegrin domain of A disintegrin and metalloproteinase 15.
abstract: A disintegrin and metalloproteinases (ADAMs), a family of transmembrane glycoproteins, are expressed in numerous tissues and organs, and have been implicated in a variety of physiological and pathological processes. ADAM15 is unique among the ADAMs in having an Arg-Gly-Asp motif in its disintegrin domain. In the present study, the antitumor and anti-angiogenic effects of the recombinant human disintegrin domain (rhdd) ADAM15, expressed by Escherichia coli, were evaluated. rhddADAM15 inhibited the proliferation and migration of several tumor cells, with a half maximal inhibitory concentration of 1.0-6.0 µM. In addition, rhddADAM15 inhibited the proliferation of Bel-7402 cells via the mitogen-activated protein kinase pathway and reduced the activation of Src. rhddADAM15 (1-10 µM) inhibited the proliferation, migration and tube formation of vascular endothelial EA.hy926 cells. G0/G1 arrest (10.96 ± 1.40%) and apoptotic cells (55.85 ± 1.06%) were observed in the EA.hy926 cells treated with 4 µM and 6 µM rhddADAM15, respectively. In vivo, rhddADAM15 significantly inhibited angiogenesis in zebrafish. rhddADAM15 at concentrations of 20 nmol/fish or 5 nmol/fish inhibited the angiogenesis of subintestinal and intersegmental vessels in the zebrafish by 72 ± 1.26 and 48 ± 2.92%, respectively. In conclusion, the results of the present study identified rhddADAM15 as a potent inhibitor of tumor formation and angiogenesis, rendering it a promising tool for use in anticancer treatment.
authors.affiliation: Laboratory of Molecular Pharmacology and Drug Design, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Chu
authors.affiliation: Laboratory of Molecular Pharmacology and Drug Design, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Laboratory of Molecular Pharmacology and Drug Design, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Lei
authors.affiliation: Laboratory of Molecular Pharmacology and Drug Design, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Pharmacology and Drug Design, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Laboratory of Molecular Pharmacology and Drug Design, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Xiaohai
authors.initials: X
authors.lastname: Gong
authors.affiliation: Laboratory of Molecular Pharmacology and Drug Design, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Laboratory of Molecular Pharmacology and Drug Design, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005786:Gene Expression Regulation; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007797:Laminin / Q000737:chemistry; D061986:MCF-7 Cells; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011509:Proteoglycans / Q000737:chemistry; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015027:Zebrafish; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D007797:Laminin; D008565:Membrane Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; C059485:matrigel; D003094:Collagen; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases; D051722:ADAM Proteins; C098660:ADAM15 protein, human