title: ACTIBIND, a T2 RNase, competes with angiogenin and inhibits human melanoma growth, angiogenesis, and metastasis.
abstract: Melanoma is a very aggressive and highly angiogenic tumor in which standard treatments have had only limited success. Patients with advanced disease have a 5-year survival rate of 5%. In search for alternatives, we identified a natural product extracted from the fungus Aspergillus niger, termed ACTIBIND, that inhibits tumor growth and metastasis of melanoma in vivo. ACTIBIND, a T2 RNase, exerts antitumorigenic and antiangiogenic activities by competing with the angiogenic factor angiogenin (itself an RNase homologue). Thus, there was decreased expression and activity of the matrix metalloproteinase 2 in melanoma and vascular endothelial cells, decreased vascularization, and increased tumor cell apoptosis in vivo. ACTIBIND significantly inhibited angiogenesis in an in vivo angiogenesis assay with sponges containing angiogenin. In vitro, ACTIBIND was internalized by both melanoma and human umbilical vein endothelial cells, reached the cell nuclei, and inhibited the activity of angiogenin response elements in a dose-dependent manner. Collectively, our data indicate that ACTIBIND should be tested for its potential as a new antiangiogenic modality for the treatment of melanoma.
authors.affiliation: The Institute of Biochemistry, Food Science, and Nutrition, Faculty of Agricultural, Food, and Environmental Quality Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Betty
authors.initials: B
authors.lastname: Schwartz
authors.forename: Oded
authors.initials: O
authors.lastname: Shoseyov
authors.forename: Vladislava O
authors.initials: VO
authors.lastname: Melnikova
authors.forename: Marya
authors.initials: M
authors.lastname: McCarty
authors.forename: Michael
authors.initials: M
authors.lastname: Leslie
authors.forename: Levava
authors.initials: L
authors.lastname: Roiz
authors.forename: Patricia
authors.initials: P
authors.lastname: Smirnoff
authors.forename: Guo-Fu
authors.initials: GF
authors.lastname: Hu
authors.forename: Dina
authors.initials: D
authors.lastname: Lev
authors.forename: Menashe
authors.initials: M
authors.lastname: Bar-Eli
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001234:Aspergillus niger / Q000201:enzymology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004347:Drug Interactions; D004722:Endoribonucleases / Q000378:metabolism / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D008156:Luciferases; D004722:Endoribonucleases; C046366:angiogenin; C022543:ribonuclease T(2); D012259:Ribonuclease, Pancreatic; D020778:Matrix Metalloproteinase 2