Pharmacological inhibition of poly(ADP-ribose) polymerase inhibits angiogenesis.
Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme which plays an important role in regulating cell death and cellular responses to DNA repair. Pharmacological inhibitors of PARP are being considered as treatment for cancer both in monotherapy as well as in combination with chemotherapeutic agents and radiation, and were also reported to be protective against untoward effects exerted by certain anticancer drugs. Here we show that pharmacological inhibition of PARP with 3-aminobenzamide or PJ-34 dose-dependently reduces VEGF-induced proliferation, migration, and tube formation of human umbilical vein endothelial cells in vitro. These results suggest that treatment with PARP inhibitors may exert additional benefits in various cancers and retinopathies by decreasing angiogenesis.
Rajesh
Mohanraj
M
Section On Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, NIAAA, National Institutes of Health, 5625 Fishers Lane, MSC-9413, Bethesda, MD 20892-9413, USA.
Mukhopadhyay
Partha
P
Bátkai
Sándor
S
Godlewski
Grzegorz
G
Haskó
György
G
Liaudet
Lucas
L
Pacher
Pál
P
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D010616:Phenanthrenes / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D001549:Benzamides; D004791:Enzyme Inhibitors; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C025160:3-aminobenzamide