RNA damage and inhibition of neoplastic endothelial cell growth: Effects of human and amphibian ribonucleases

Angiogenesis defines the many steps involved in the growth and migration of endothelial cell-derived blood vessels, This process is necessary for the growth and metastasis of tumors, and considerable effort is being expended to find inhibitors of tumor angiogenesis. This usually involves screening o f potential anti-angiogenic compounds on endothelial cells, To this end, tw o candidate anti-angiogenic RNA-damaging agents, onconase and (-4)rhEDN, we re screened for their effects on endothelial cell proliferation using three distinct types of endothelial cells in culture: HPV-16 E6/E7-immortalized human umbilical vein endothelial cells (HUVECs), a Kras-transformed HPV-16 E6/E7 HUVEC (Rhim et at, Carcinogenesis 4, 673-681, 1998), and primary HUVE Cs. Onconase similarly inhibited proliferation in all three cell lines (IC5 0 = 0.3-1.0 muM) while (-4)rhEDN was more effective on immortalized HUVEC c ell lines (IC50 = 0.02-0.06 muM) than on primary HUVECs (IC50 > 0.1 muM). D ifferential sensitivity to these agents implies that more than one endothel ial cell type must be used in proliferation assays to screen for novel anti -angiogenic compounds. (C) 2001 by Radiation Research Society.