Antitumor and anti-angiogenic activity of the recombinant human disintegrin domain of A disintegrin and metalloproteinase 15.

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.