Low doses of 3-aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, stimulate angiogenesis by regulating expression of urokinase type plasminogen activator and matrix metalloprotease 2

Human umbilical vein endothelial cells were treated with 3 aminobenzamide (3ABA), a PARP inhibitor, and tested for several different cellular parameters.Here we present in vitro evidence that a low concentration of 3ABA (50 μM), stimulates angiogenesis by decreasing fibrinolytic activity, carried out by urokinase-type plasminogen activator (uPA), and by enhancing matrix metalloprotease-2 (MMP-2) gelatinolytic activity, in fibroblast growth factor-2-stimulated endothelial cells. These unbalanced pathways modify in vitro angiogenic steps, inhibiting chemoinvasion and stimulating tubulogenic activity.Our results suggest that the proangiogenic effect of low concentrations of 3ABA alerts on the efficacy of PARP inhibitors to potentiate anticancer therapy. Moreover, they indicate that endothelial chemoinvasion and tubulogenesis depend on distinct proteolytic pathways.Angiogenesis, the process of formation of new blood vessels from preexisting capillaries, is essential for normal development in embryos. In adults, with some exceptions like the female reproductive cycle and the granular tissue in wound healing processes, angiogenesis is an undesired process in certain pathological conditions: in rheumatoid arthritis, in psoriasis, in diabetic retinopathy, in the enlarging atherosclerosis plaque, and in other pathologic phenomena including cancer [1]. In particular, the growth of capillaries into tumors leads to their enlargement and helps the tumor cells to metastasize. Angiogenesis requires endothelial cells to migrate, proliferate, and ultimately assemble into tubes that regulate selective transport of blood cells and solutes from their lumen to the interstitium and vice versa.Endothelial cell survival and proliferation are a prerequisite for migration, sprouting and tubulogenesis. Endothelial cell proliferation is stimulated by a number of soluble factors and cytokines including fibroblast growth factor (FGF). The basic form (FGF2) is known to be a strong migration, spro