Mitochondrial function is controlled by melatonin and its metabolites in vitro in human melanoma cells.

Abstract

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 (N1 -acetyl-N2 -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.

• Authors: Bernadetta Bilska, Fiona Schedel, Anna Piotrowska, Joanna Stefan, Michal Zmijewski, Elżbieta Pyza, Russel J Reiter, Kerstin Steinbrink, Andrzej T Slominski, Meri K Tulic, Konrad Kleszczyński
• Journal: Journal of pineal research (J Pineal Res) Vol. 70 Issue 3 Pg. e12728 (Apr 2021) ISSN: 1600-079X [Electronic] England
• PMID: 33650175 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Journal of Pineal Research published by John Wiley & Sons Ltd.

Chemical References

• Antineoplastic Agents
• Melatonin

Topics

• Antineoplastic Agents (metabolism, pharmacology)
• Biotransformation
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Energy Metabolism (drug effects)
• Humans
• Melanoma (drug therapy, metabolism, pathology)
• Melatonin (metabolism, pharmacology)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism, pathology)
• Oxidative Stress (drug effects)
• Skin Neoplasms (drug therapy, metabolism, pathology)