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Mitochondrial function is controlled by melatonin and its metabolites in vitro in human melanoma cells
Author(s) -
Bilska Bernadetta,
Schedel Fiona,
Piotrowska Anna,
Stefan Joanna,
Zmijewski Michal,
Pyza Elżbieta,
Reiter Russel J.,
Steinbrink Kerstin,
Slominski Andrzej T.,
Tulic Meri K.,
Kleszczyński Konrad
Publication year - 2021
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12728
Subject(s) - melatonin , melanoma , oxidative phosphorylation , melanin , biology , bioenergetics , mitochondrion , glycolysis , cancer research , in vitro , programmed cell death , melanocyte , pharmacology , biochemistry , apoptosis , endocrinology , metabolism
Melanoma is a leading cause of cancer deaths worldwide. Although immunotherapy has revolutionized the treatment for some patients, resistance towards therapy and unwanted side effects remain a problem for numerous individuals. Broad anti‐cancer activities of melatonin are recognized; however, additional investigations still need to be elucidated. Herein, using various human melanoma cell models, we explore in vitro the new insights into the regulation of melanoma by melatonin and its metabolites which possess, on the other side, high safety profiles and biological meaningful. In this study, using melanotic (MNT‐1) and amelanotic (A375, G361, Sk‐Mel‐28) melanoma cell lines, the comparative oncostatic responses, the impact on melanin content (for melanotic MNT‐1 melanoma cells) as well as the mitochondrial function controlled by melatonin, its precursor (serotonin), a kynuric ( N 1 ‐acetyl‐ N 2 ‐formyl‐5‐methoxykynuramine, AFMK) and indolic pathway (6‐hydroxymelatonin, 6(OH)MEL and 5‐methoxytryptamine, 5‐MT) metabolites were assessed. Namely, significant disturbances were observed in bioenergetics as follows: ( i ) uncoupling of oxidative phosphorylation (OXPHOS), ( ii ) attenuation of glycolysis, ( iii ) dissipation of mitochondrial transmembrane potential (mtΔΨ) accompanied by ( iv ) massive generation of reactive oxygen species (ROS), and ( v ) decrease of glucose uptake. Collectively, these results together with previously published reports provide a new biological potential and make an imperative to consider using melatonin or its metabolites for complementary future treatments of melanoma‐affected patients; however, these associations should be additionally investigated in clinical setting.