Year: 2023
Type: article
Abstract: Melatonin (N-acetyl-5-methoxytryptamine, MEL), its kynurenic (N1-acetyl-N2-formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and 5-methoxytryptamine, 5-MT) are endogenously produced in human epidermis. Melatonin, produced by the pineal gland, brain and peripheral organs, displays a diversity of physiological functions including anti-inflammatory, immunomodulatory, and anti-tumor capacities. Herein, we assessed their regulatory effect on melanogenesis using amelanotic (A375, Sk-Mel-28) and highly pigmented (MNT-1, melanotic) human melanoma cell lines. We discovered that subjected compounds decrease the downstream pathway of melanin synthesis by causing a significant drop of cyclic adenosine monophosphate (cAMP) level, the microphthalmia-associated transcription factor (MITF) and resultant collapse of tyrosinase (TYR) activity, and melanin content comparatively to N-phenylthiourea (PTU, a positive control). We observed a reduction in pigment in melanosomes visualized by the transmission electron microscopy. Finally, we assessed the role of G-protein-coupled seven-transmembrane-domain receptors. Obtained results revealed that nonselective MT1 and MT2 receptor antagonist (luzindole) or selective MT2 receptor antagonist (4-P-PDOT) did not affect dysregulation of the melanin pathway indicating a receptor-independent mechanism. Our findings, together with the current state of the art, provide a convenient experimental model to study the complex relationship between metabolites of melatonin and the control of pigmentation serving as a future and rationale strategy for targeted therapies of melanoma-affected patients.
Institutions: University of Münster, University of Miami, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Jagiellonian University, The University of Texas at San Antonio Health Science Center, Inserm, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire, University of Alabama at Birmingham, Birmingham VA Medical Center
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,780
Awards: G124267032, SFB 1450: Darstellung organspezifischer Entzündung durch multiskalige Bildgebung, G2098817112, SFB 1066: Nanodimensionale polymere Therapeutika für die Tumortherapie, SFB 1009: Breaking Barriers Immunzellen und pathogene Erreger an Zell/MatrixBarrieren, G4553016885, TRR 156: Die Haut als Sensor und Initiator von lokaler und systemischer Immunität, Significance of metabolic activation of lumisterol in the skin, G5698286025, G6433949306, G797723098, Mechanism of action and function of novel secosteroid 20(OH)D3 in the skin
OpenAlex ID: W4387401293