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.

中文翻译：

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人黑色素瘤细胞体外线粒体功能受褪黑激素及其代谢物控制

黑色素瘤是全球癌症死亡的主要原因。尽管免疫疗法已经彻底改变了一些患者的治疗方法，但对治疗的抵抗和不必要的副作用仍然是许多人面临的问题。褪黑激素的广泛抗癌活性得到认可；然而，仍需要阐明进一步的调查。在这里，我们使用各种人类黑色素瘤细胞模型，在体外探索了褪黑激素及其代谢物对黑色素瘤调节的新见解，另一方面，这些物质具有高安全性和生物学意义。在这项研究中，使用黑色素 (MNT-1) 和黑色素 (A375、G361、Sk-Mel-28) 黑色素瘤细胞系，比较肿瘤抑制反应，对黑色素含量的影响（对于黑色素 MNT-1 黑色素瘤细胞）以及由褪黑激素控制的线粒体功能，评估了N ^1-乙酰基-N ^2-甲酰基-5-甲氧基犬尿胺，AFMK）和吲哚途径（6-羟基褪黑激素，6（OH）MEL 和 5-甲氧基色胺，5-MT）代谢物。即，在生物能量学中观察到如下显着干扰：（i）氧化磷酸化（OXPHOS）的解偶联，（ii）糖酵解的减弱，（iii）线粒体跨膜电位（mtΔΨ）的耗散伴随（iv）大量产生的活性氧物种 (ROS) 和 ( v) 葡萄糖摄取减少。总的来说，这些结果与之前发表的报告一起提供了新的生物学潜力，并迫切需要考虑使用褪黑激素或其代谢物来补充未来对黑色素瘤患者的治疗；然而，这些关联应在临床环境中进行额外研究。