Melatonin: A Potential Regulator of DNA Methylation

The pineal gland-derived indoleamine hormone, melatonin, regulates multiple cellular processes, ranging from chronobiology, proliferation, apoptosis, and oxidative damage to pigmentation, immune regulation, and mitochondrial metabolism. While melatonin is best known as a master regulator of the circadian rhythm, previous studies also have revealed connections between circadian cycle disruption and genomic instability, including epigenetic changes in the pattern of DNA methylation. For example, melatonin secretion is associated with differential circadian gene methylation in night shift workers and the regulation of genomic methylation during embryonic development, and there is accumulating evidence that melatonin can modify DNA methylation. Since the latter one impacts cancer initiation, and also, non-malignant diseases development, and that targeting DNA methylation has become a novel intervention target in clinical therapy, this review discusses the potential role of melatonin as an under-investigated candidate epigenetic regulator, namely by modulating DNA methylation via changes in mRNA and the protein expression of DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins. Furthermore, since melatonin may impact changes in the DNA methylation pattern, the authors of the review suggest its possible use in combination therapy with epigenetic drugs as a new anticancer strategy.

Automated summary

The indoleamine hormone melatonin, derived from the pineal gland, regulates various cellular processes including the circadian rhythm, proliferation, apoptosis, oxidative damage, immune regulation, pigmentation, and mitochondrial metabolism. Melatonin has been shown to have effects on DNA methylation, which is involved in cancer initiation and non-malignant diseases development. This review discusses the potential role of melatonin as an epigenetic regulator by modulating DNA methylation through changes in the expression of DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins. The authors suggest that melatonin could be used in combination with epigenetic drugs as a new anticancer strategy.