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 of potential anti-angiogenic compounds on endothelial cells. To this end, two candidate anti-angiogenic RNA-damaging agents, onconase and (-4)rhEDN, were 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 al., Carcinogenesis 4, 673-681, 1998), and primary HUVECs. Onconase similarly inhibited proliferation in all three cell lines (IC(50) = 0.3-1.0 microM) while (-4)rhEDN was more effective on immortalized HUVEC cell lines (IC(50) = 0.02-0.06 microM) than on primary HUVECs (IC(50) > 0.1 microM). Differential sensitivity to these agents implies that more than one endothelial cell type must be used in proliferation assays to screen for novel anti-angiogenic compounds.
Newton
D L
DL
SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
Kaur
G
G
Rhim
J S
JS
Sausville
E A
EA
Rybak
S M
SM
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004527:Egg Proteins / Q000494:pharmacology* / Q000633:toxicity; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D047208:Eosinophil-Derived Neurotoxin; D006131:Growth Inhibitors / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011506:Proteins / Q000494:pharmacology* / Q000633:toxicity; D012313:RNA / Q000187:drug effects / Q000378:metabolism; D011894:Rana pipiens; D011994:Recombinant Proteins / Q000494:pharmacology; D012259:Ribonuclease, Pancreatic / Q000494:pharmacology* / Q000633:toxicity; D012260:Ribonucleases / Q000494:pharmacology* / Q000633:toxicity
D020533:Angiogenesis Inhibitors; D004527:Egg Proteins; D006131:Growth Inhibitors; D011506:Proteins; D011994:Recombinant Proteins; D012313:RNA; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases; D012259:Ribonuclease, Pancreatic; C058703:ranpirnase