Vascular endothelial growth factor (VEGF) and melanoma. N-acetylcysteine downregulates VEGF production in vitro

Vascular endothelial growth factor (VEGF), the most potent angiogenic facto r identified to date, is associated with growth and metastasis of solid tum ours, including melanoma, It has been shown in vitro that melanoma cells pr oduce raised concentrations of VEGF, We examined the VEGF concentrations in plasma of 20 patients with primary melanoma, local recurrence and metastat ic melanoma. We also studied the inhibiting effect of one antioxidant, N-ac etylcysteine, on VEGF production in three human melanoma cell lines, We fou nd elevated levels of VEGF (median 205 pg mi; 95 percent confidence interva l, 80-414) in metastatic melanoma,,vith respect to primary and locally recu rrent melanoma (75 pg/ml; 95 percent confidence interval, 35-130), The heal th control patients had Iel eis of 25 pg/ml (95 percent confidence interval , 10-35), Human melanoma cell lines secreted VEGF in basal conditions (550- 963 +/- 125 pg/ml) and N-acetylcysteine (0.5-20 mM) significantly decreased the VEGF production in a dose-dependent manner. VEGF concentrations were f ound to he raised in patients with primary melanoma, local recurrence, and above all, metastatic melanoma (P=0.008), N-acetylcysteine inhibits VEGF pr oduction in three human melanoma cell lines. This antioxidant might have th erapeutic applications in metastatic melanoma in combination with other cyt otoxic drugs. (C) 2000 Academic Press.