Differentiation induced by 3-aminobenzamide, a poly(ADP- ribose) polymerase inhibitor, in transformed endothelial cells

Poly(ADP-ribosyl)ation of proteins is an important switch in cellular processes including differentiation. In particular, recent advances reveal emerging role in differentiation of cancer cells. Here we described the effect of poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide on a morphological feature of differentiation in transformed endothelial cells GM7373. Exposed to this drug, the cells displayed a 40% growth inhibition due to apoptosis, valued by time-lapse videomicroscopy and TUNEL assay. At the same time, cells showed enhanced motility and, when cultured on Matrigel enriched with FGF2 plus 3-aminobenzamide, began to organize a capillary network, in an Akt phosphorylation dependent manner, accompanied by a cyclooxygenase-2 induction. These results validate the role of poly(ADP-ribose) polymerase activity in cell differentiation and confirm the hypothesis that PARP may be a useful target for anticancer drugs.