Melatonin and Its Metabolites Ameliorate UVR-Induced Mitochondrial Oxidative Stress in Human MNT-1 Melanoma Cells

Abstract

Melatonin (Mel) is the major biologically active molecule secreted by the pineal gland. Mel and its metabolites, 6-hydroxymelatonin (6(OH)Mel) and 5-methoxytryptamine (5-MT), possess a variety of functions, including the scavenging of free radicals and the induction of protective or reparative mechanisms in the cell. Their amphiphilic character allows them to cross cellular membranes and reach subcellular organelles, including the mitochondria. Herein, the action of Mel, 6(OH)Mel, and 5-MT in human MNT-1 melanoma cells against ultraviolet B (UVB) radiation was investigated. The dose of 50 mJ/cm2 caused a significant reduction of cell viability up to 48%, while investigated compounds counteracted this deleterious effect. UVB exposure increased catalase activity and led to a simultaneous Ca++ influx (16%), while tested compounds prevented these disturbances. Additional analysis focused on mitochondrial respiration performed in isolated mitochondria from the liver of BALB/cJ mice where Mel, 6(OH)Mel, and 5-MT significantly enhanced the oxidative phosphorylation at the dose of 10−6 M with lower effects seen at 10−9 or 10−4 M. In conclusion, Mel, 6(OH)Mel and 5-MT protect MNT-1 cells, which express melatonin receptors (MT1 and MT2) against UVB-induced oxidative stress and mitochondrial dysfunction, including the uncoupling of oxidative phosphorylation.

Melatonin exerts oncostatic capacity and decreases melanogenesis in human MNT‐1 melanoma cells

“…It neutralizes pigmentation disturbances mediated by exogenously applied melanogenic inhibitors. The molecular mode of action of melatonin may be related to the fact that it tends to maintain cellular homeostasis as observed earlier when it attenuates oxidative stress,, apoptosis and inflammation in normal cells while stimulating it in cancer cells. Herein, melatonin's action on pigmentation opens new regulatory targets for this molecule.…”

Characterization of serotonin and N‐acetylserotonin systems in the human epidermis and skin cells

“…Normal neonatal human melanocytes (Cell Applications, Inc) were cultured in melanocyte medium (Medium254) supplemented with human melanocyte growth supplement (HMGS) (Thermo Fisher Scientific). MNT‐1 cells were maintained in DMEM supplemented with 20% ( v / v ) heat‐inactivated fetal bovine serum, 2 mM L‐glutamine, 10 mM HEPES, 1 mM sodium pyruvate, 1% ( v / v ) NEAA, and 1% ( v / v ) streptomycin‐penicillin solution at 37°C in a humidified atmosphere of 5% CO 2 in air . Cells in the logarithmic growth phase were used in all experiments, while 80%‐90% monolayers of confluent MNT‐1 cells were harvested with a mixture of 0.05% trypsin‐EDTA solution.…”

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

“…Melatonin is a naturally occurring molecule assumed to be present in every species [ 19 ]. Due to its antioxidant, anti-inflammatory, as well as other properties [ 20 , 21 , 22 , 23 , 24 , 25 ], it has been speculated to be a promising molecule for treating COVID-19 patients [ 18 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ], and also other deadly viral infectious diseases [ 48 , 49 , 50 , 51 ]. A small scale clinical trial has also shown promising results [ 52 ].…”