Effects of melatonin, its precursors and derivatives on the growth of cultured 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 cells were plated into 24-well plates. Melatonin, its 6-hydroxy or 6-chloro derivative, serotonin, tryptophan or kynurenine was added to the medium in concentrations of 0.001 to 1000 nM. After 5 days the cells were detached, counted, and compared with the controls. Melatonin inhibited the growth of uveal melanoma cell lines in a dose-dependent manner (0.1-10 nM). This growth inhibition occurred at concentrations of melatonin (2 nM) found in human aqueous humour. The melatonin derivatives also inhibited the growth of uveal melanoma cells; 6-chloromelatonin was more potent than melatonin and 6-hydroxymelatonin was the least active (6-chloromelatonin > melatonin > 6-hydroxymelatonin). The precursors 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 melatonin may play a role in the pathogenesis of uveal melanoma.
Department of Pathology, New York Eye and Ear Infirmary, NY 10003, USA.
D N
DN
Hu
S A
SA
McCormick
J E
JE
Roberts
D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007737:Kynurenine / Q000494:pharmacology; D008545:Melanoma / Q000473:pathology*; D008550:Melatonin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000473:pathology*
D012701:Serotonin; D007737:Kynurenine; C024100:6-chloromelatonin; D014364:Tryptophan; D008550:Melatonin; C012365:6-hydroxymelatonin