Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells
Melatonin (<i>N</i>-acetyl-5-methoxytryptamine, MEL), its kynurenic (<i>N</i><sup>1</sup>-acetyl-<i>N</i><sup>2</sup>-formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and 5-methoxytryptamine, 5-MT) are...
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/19/14947 |
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| author | Jack K. S. Möller Kinga Linowiecka Maciej Gagat Anna A. Brożyna Marek Foksiński Agnieszka Wolnicka-Glubisz Elżbieta Pyza Russel J. Reiter Meri K. Tulic Andrzej T. Slominski Kerstin Steinbrink Konrad Kleszczyński |
| author_facet | Jack K. S. Möller Kinga Linowiecka Maciej Gagat Anna A. Brożyna Marek Foksiński Agnieszka Wolnicka-Glubisz Elżbieta Pyza Russel J. Reiter Meri K. Tulic Andrzej T. Slominski Kerstin Steinbrink Konrad Kleszczyński |
| author_sort | Jack K. S. Möller |
| collection | DOAJ |
| description | Melatonin (<i>N</i>-acetyl-5-methoxytryptamine, MEL), its kynurenic (<i>N</i><sup>1</sup>-acetyl-<i>N</i><sup>2</sup>-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 <i>N</i>-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. |
| first_indexed | 2024-03-10T21:43:09Z |
| format | Article |
| id | doaj.art-d3f3ebafbb9d4d1ebbbdb53a90b8a928 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:43:09Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d3f3ebafbb9d4d1ebbbdb53a90b8a9282023-11-19T14:32:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124191494710.3390/ijms241914947Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma CellsJack K. S. Möller0Kinga Linowiecka1Maciej Gagat2Anna A. Brożyna3Marek Foksiński4Agnieszka Wolnicka-Glubisz5Elżbieta Pyza6Russel J. Reiter7Meri K. Tulic8Andrzej T. Slominski9Kerstin Steinbrink10Konrad Kleszczyński11Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, GermanyDepartment of Human Biology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Lwowska 1, 87-100 Toruń, PolandDepartment of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, PolandDepartment of Human Biology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Lwowska 1, 87-100 Toruń, PolandDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, PolandDepartment of Biophysics and Cancer Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, PolandDepartment of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Kraków, PolandDepartment of Cell Systems and Anatomy, UT Health, Long School of Medicine, San Antonio, TX 78229, USATeam 12, INSERM U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Université Côte d’Azur, 06200 Nice, FranceDepartment of Dermatology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, GermanyDepartment of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, GermanyMelatonin (<i>N</i>-acetyl-5-methoxytryptamine, MEL), its kynurenic (<i>N</i><sup>1</sup>-acetyl-<i>N</i><sup>2</sup>-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 <i>N</i>-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.https://www.mdpi.com/1422-0067/24/19/14947melatoninmelanogenesiskynurenic and indolic metabolitestyrosinasehuman melanomaG-protein-coupled membrane receptors |
| spellingShingle | Jack K. S. Möller Kinga Linowiecka Maciej Gagat Anna A. Brożyna Marek Foksiński Agnieszka Wolnicka-Glubisz Elżbieta Pyza Russel J. Reiter Meri K. Tulic Andrzej T. Slominski Kerstin Steinbrink Konrad Kleszczyński Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells International Journal of Molecular Sciences melatonin melanogenesis kynurenic and indolic metabolites tyrosinase human melanoma G-protein-coupled membrane receptors |
| title | Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells |
| title_full | Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells |
| title_fullStr | Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells |
| title_full_unstemmed | Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells |
| title_short | Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells |
| title_sort | melanogenesis is directly affected by metabolites of melatonin in human melanoma cells |
| topic | melatonin melanogenesis kynurenic and indolic metabolites tyrosinase human melanoma G-protein-coupled membrane receptors |
| url | https://www.mdpi.com/1422-0067/24/19/14947 |
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