Antiapoptotic and antigenotoxic effects of N-acetylcysteine in human cells of endothelial origin.
N-Acetylcysteine (NAC) is a drug bearing multiple preventive properties that can inhibit genotoxicity and carcinogenicity. NAC also inhibits invasion and metastasis of malignant cells, as well as tumor take. We recently demonstrated the effects of NAC on Kaposi's sarcoma cells supernatant-induced invasion in vitro and angiogenesis in vivo. Many anticancer agents act through cytotoxicity of rapidly proliferating cells and several antineoplastic drugs induce apoptosis of cancer cells. Since endothelial cells are the target for the inhibition of angiogenesis, we wanted to verify that NAC, while inhibiting tumor vascularization and endothelial cell invasion would not induce endothelial cell apoptosis. We tested the ability of NAC to modulate apoptosis 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, appears to prevent apoptosis and oxygen-related genotoxicity in endothelial cells.
Aluigi
M G
MG
Advanced Biotechnology Center, Genoa, Italy.
De Flora
S
S
D'Agostini
F
F
Albini
A
A
Fassina
G
G
D000111:Acetylcysteine / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D016587:Antimutagenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D016587:Antimutagenic Agents; D016212:Transforming Growth Factor beta; D019328:Buthionine Sulfoximine; D010269:Paraquat; D000111:Acetylcysteine