EFFECTS OF MELATONIN, ITS PRECURSORS AND DERIVATIVES ON THE GROWTH OFCULTURED HUMAN UVEAL MELANOMA-CELLS

The effects of melatonin, its precursors and derivatives on the growth of cultured human uveal melanoma cells were studied. The melanoma cel ls were plated into 24-well plates. Melatonin, its 6-hydroxy or 6-chlo ro derivative, serotonin, tryptophan or kynurenine was added to the me dium in concentrations of 0.001 to 1000 nM, After 5 days the cells wer e detached, counted, and compared with the controls. Melatonin inhibit ed the growth of uveal melanoma cell lines in a dose-dependent manner (0.1-10 nM). This growth inhibition occurred at concentrations of mela tonin (2 nM) found in human aqueous humour, The melatonin derivatives also inhibited the growth of uveal melanoma cells; 6-chloromelatonin w as more potent than melatonin and 6-hydroxymelatonin was the least act ive (6-chloromelatonin > melatonin > 6-hydroxymelatonin), The precurso rs of melatonin (tryptophan and serotonin) and the abnormal metabolite of tryptophan (kynurenine) did not inhibit the growth of the melanoma cells, indicating that changes to the metabolic processes of melatoni n may play a role in the pathogenesis of uveal melanoma. (C) 1998 Lipp incott-Raven Publishers.