Antiapoptotic and antigenotoxic effects of N-acetylcysteine in human cellsof endothelial origin

N-Acetylcysteine (NAC) is a drug bearing multiple preventive properties tha t can inhibit genotoxicity and carcinogenicity. NAC also inhibits invasion and metastasis of malignant cells, as well as tumor take. We recently demon strated the effects of NAC on Kaposi's sal coma cells supernatant-induced i nvasion in vitro and angiogenesis in vivo. Many anticancer agents act throu gh cytotoxicity of rapidly proliferating cells and several antineoplastic d rugs induce apoptosis of cancel cells. Since endothelial cells are the targ et for the inhibition of angiogenesis, we wanted to verify that NAC, while inhibiting tumor vascularization and endothelial cell invasion would not in duce endothelial cell apoptosis. We tested the ability of NAC to modulate a poptosis and cytogenetic damage in vitro and to promote differentiation on a reconstituted basement membrane (matrigel) in two endothelial cell lines (EAhy926 and HUVE). Treatment with NAC protected endothelial cells from TGF -beta -induced apoptosis and paraquat-induced cytogenetic damage. Therefore , NAC acts as an antiangiogenic agent and, at the same time, appeals to pl event apoptosis and oxygen-related genotoxicity in endothelial cells.