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

Vascular endothelial growth factor (VEGF), the most potent angiogenic factor identified to date, is associated with growth and metastasis of solid tumours, including melanoma, It has been shown in vitro that melanoma cells produce raised concentrations of VEGF, We examined the VEGF concentrations in plasma of 20 patients with primary melanoma, local recurrence and metastatic melanoma. We also studied the inhibiting effect of one antioxidant, N-acetylcysteine, on VEGF production in three human melanoma cell lines, We found elevated levels of VEGF (median 205 pg mi; 95 percent confidence interval, 80-414) in metastatic melanoma,,vith respect to primary and locally recurrent melanoma (75 pg/ml; 95 percent confidence interval, 35-130), The health 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 found to he raised in patients with primary melanoma, local recurrence, and above all, metastatic melanoma (P=0.008), N-acetylcysteine inhibits VEGF production in three human melanoma cell lines. This antioxidant might have therapeutic applications in metastatic melanoma in combination with other cytotoxic drugs. (C) 2000 Academic Press.