Melatonin decreases cell proliferation and induces melanogenesis in human melanoma SK-MEL-1 cells.
Melatonin is an indoleamine synthesized in the pineal gland, and after its release into the blood, it has an extensive repertoire of biological activities, including antitumoral properties. In this study, we found that melatonin reduced the growth of the human melanoma cells SK-MEL-1. The antiproliferative effect was associated with an alteration in the progression of the phases of the cell cycle and also with an increase in tyrosinase activity, the key regulatory enzyme of melanogenesis. Antagonists for melatonin membrane receptors (luzindole and 4-P-PDOT) and the general G-coupled receptor inhibitor, pertussis toxin, did not prevent the melatonin-induced cell growth arrest; this suggests a mechanism independent of G-coupled membrane receptors. In contrast, p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway seems to play a significant role in cell growth inhibition by melatonin. The indoleamine-induced phosphorylation of p38 MAPK and the effect on cell proliferation were abrogated by the specific inhibitor SB203580. Furthermore, comparative studies with known antioxidants such as N-acetyl-l-cysteine and trolox indicate that the growth of SK-MEL-1 cells is highly sensitive to antioxidants.
Cabrera
Javier
J
Departamento de Ciencias Clínicas, Facultad de Ciencias de la Salud, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
Negrín
Gledy
G
Estévez
Francisco
F
Loro
Juan
J
Reiter
Russel J
RJ
Quintana
José
J
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C114459:4-phenyl-2-propionamidotetraline; D004224:Diterpenes; D044094:Receptors, Melatonin; D013764:Tetrahydronaphthalenes; C505295:luzodiol; D048051:p38 Mitogen-Activated Protein Kinases; D008550:Melatonin