{"doi":"10.3390/ijms241914947","title":"Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells","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.","journal":"International Journal of Molecular Sciences","year":2023,"id":362958,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9651,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":94305,"name":"Kinga Linowiecka","orcid":"0000-0002-7029-2657","position":1,"is_corresponding":false},{"id":1071515,"name":"Maciej Gagat","orcid":"0000-0002-5445-8821","position":2,"is_corresponding":false},{"id":94308,"name":"Anna A. Brożyna","orcid":"0000-0002-3195-9965","position":3,"is_corresponding":false},{"id":1116491,"name":"Marek Foksiński","orcid":"0000-0002-1338-8230","position":4,"is_corresponding":false},{"id":94306,"name":"Agnieszka Wolnicka-Głubisz","orcid":"0000-0003-3070-6349","position":5,"is_corresponding":false},{"id":881671,"name":"Elżbieta Pyza","orcid":"0000-0003-1503-9533","position":6,"is_corresponding":false},{"id":618604,"name":"Rüssel J. Reiter","orcid":"0000-0001-6763-4225","position":7,"is_corresponding":false},{"id":760555,"name":"Meri K. Tulić","orcid":"0000-0002-2661-2369","position":8,"is_corresponding":false},{"id":97237,"name":"Andrzej Słomiński","orcid":"0000-0001-8963-3995","position":9,"is_corresponding":false},{"id":760554,"name":"Kerstin Steinbrink","orcid":"0000-0002-0500-2158","position":10,"is_corresponding":false},{"id":483014,"name":"Konrad Kleszczyński","orcid":"0000-0002-1311-263X","position":11,"is_corresponding":false},{"id":1116969,"name":"Jack K. S. Möller","orcid":null,"position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T01:14:23.749325Z","pmid":"37834395","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}