Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, Kraków, Poland.
Department of Dermatology, University of Münster, Münster, Germany.
J Pineal Res. 2021 Apr;70(3):e12728. doi: 10.1111/jpi.12728. Epub 2021 Mar 14.
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 -acetyl-N -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.
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，但对许多人来说，对治疗的耐药性和不良副作用仍然是一个问题。褪黑素具有广泛的抗癌活性已得到认可；然而，仍需要进一步研究。在此，我们使用各种人黑色素瘤细胞模型，在体外探索褪黑素及其代谢物对黑色素瘤的调控的新见解，这些代谢物具有高安全性和生物学意义。在这项研究中，我们使用黑瘤（MNT-1）和无色素瘤（A375、G361、Sk-Mel-28）黑色素瘤细胞系，比较了褪黑素及其前体（血清素）、一种犬尿氨酸（N -乙酰-N -甲酰-5-甲氧基犬尿氨酸，AFMK）和吲哚途径（6-羟褪黑素，6(OH)MEL 和 5-甲氧基色胺，5-MT）代谢物对黑素瘤细胞的生长抑制作用，对黑色素含量的影响（对黑瘤 MNT-1 黑色素瘤细胞）以及线粒体功能的影响。具体而言，在生物能量学方面观察到明显的干扰：（i）氧化磷酸化解偶联，（ii）糖酵解减弱，（iii）线粒体跨膜电位（mtΔΨ）耗散，伴有（iv）大量活性氧（ROS）的产生，以及（v）葡萄糖摄取减少。总的来说，这些结果与之前的报道一起，提供了褪黑素或其代谢物的新生物学潜力，并促使人们考虑将其用于未来受黑色素瘤影响的患者的补充治疗；然而，这些关联应在临床环境中进一步研究。
