Melatonin decreases cell proliferation and induces melanogenesis in human melanoma SK-MEL-1 cells

Javier Cabrera, Gledy Negrín, Francisco Estévez, Juan Loro, Russel J. Reiter, José Quintana

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


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. 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.

Original languageEnglish (US)
Pages (from-to)45-54
Number of pages10
JournalJournal of pineal research
Issue number1
StatePublished - Aug 2010


  • SK-MEL-1
  • cell proliferation
  • melanogenesis
  • melanoma
  • melatonin
  • p38 mitogen-activated protein kinase

ASJC Scopus subject areas

  • Endocrinology


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