Anti-angiogenin activity of the peptides complementary to the receptor-binding site of angiogenin.
Angiogenesis promotes growth and metastasis of tumor cells. In this study, we have developed two peptide antagonists of human angiogenin by deducing the codes from the antisense RNA sequence corresponding to the receptor-binding site of angiogenin in either 5' --> 3' (chANG) or 3' --> 5' (chGNA) direction. chANG and chGNA peptides bind to angiogenin with specificity and high affinity (Kd approximately 44 nM) and inhibit the interaction of angiogenin with actin, which is regarded as the angiogenin-binding protein on the surface of endothelial cells. The peptides inhibit the neovascularization induced by angiogenin in the chick chorioallantoic membrane assay. The anti-angiogenic activity of the peptides is specific for angiogenin, and the peptides do not have any apparent effect on embryonic angiogenesis or the preexisting blood vessels. chANG and chGNA also inhibit the angiogenesis induced by the angiogenin-secreting PC 3 human prostate adenocarcinoma cells and have no direct effect on the proliferation as well as the adhesion of PC 3 cells to angiogenin. Therefore, the inhibition of the tumor-induced angiogenesis by the peptides is most likely caused by neutralization of the extracellular angiogenin secreted by PC 3 cells. Based on our results, chANG and chGNA peptides may be effective for treatment of various human tumors which secrete angiogenin.
Gho
Y S
YS
Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea.
Chae
C B
CB
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D006801:Humans; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016372:RNA, Antisense / Q000737:chemistry / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D012259:Ribonuclease, Pancreatic; D014407:Tumor Cells, Cultured
D000199:Actins; D010455:Peptides; D011506:Proteins; D016372:RNA, Antisense; D011956:Receptors, Cell Surface; C105154:angiogenin receptor; C046366:angiogenin; D012259:Ribonuclease, Pancreatic