ACTIBIND, an actin-binding fungal T2-RNase with antiangiogenic and anticarcinogenic characteristics

摘要: BACKGROUND ACTIBIND is an Aspergillus niger extracellular ribonuclease (T2-ribonuclease [RNase]) that possesses actin-binding activity. In plants, ACTIBIND inhibits the elongation and alters orientation of pollen tubes by interfering with intracellular actin network. The question rose whether can also affect mammalian cancer development. METHODS Cell colony formation was performed in human colon (HT-29, Caco-2, RSB), breast (ZR-75-1), ovarian (2780) cells presence or absence 1 μM ACTIBIND. HT-29 ZR-75-1 cells, effect on cell migration studied microscopic observations invasion assay through Matrigel. Tube assessed umbilical vein endothelial (HUVEC) angiogenin basic fibroblast growth factor (bFGF) (1 μg/mL each) following overnight incubation 10 athymic mouse xenograft model, were injected subcutaneously, followed subcutaneous (0.4-8 mg/mouse/injection) intraperitoneal (0.001-1 injections a rat dimethylhydrazine (DMH)-colorectal carcinogenesis released directly into via osmotic micropumps (250 μg/rat/day) given orally microcapsules (1.6 mg/rat/day). Aberrant crypt foci, tumors distal colon, tumor blood vessels examined. RESULTS ACTIBIND had anticlonogenic unrelated to its It inhibited angiogenin-induced HUVEC tube dose-responsive manner. found bind vitro. bound surfaces, leading disruption internal network inhibiting motility invasiveness Matrigel-coated filters. mice, development, either as treatment. rats, exerted preventive therapeutic effects developing colonic induced DMH. reduced degree observation. CONCLUSIONS This study indicated effective antiangiogenic anticarcinogenic factor. Cancer 2006. © 2006 American Society.