Melatonin, a hormone-like substance involved in the regulation of the circadian rhythm. It is important for goos sleep but it has also been demonstrated to protect cells against oxidative DNA damage and to inhibit tumorigenesis.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3543845/
Study results-In this study, the researchers investigated the effect of melatonin on DNA strand breaks studying breast cancer (MCF-7) and colon cancer (HCT-15) cell lines. The results demonstrated an increased DNA repair capacity after melatonin treatment. They also examined gene expression in melatonin pretreated MCF-7 cells, upon carcinogen exposure and they detected an alteration in gene expression in the genes involved in DNA damage responding pathways. The conclusions made from their data were that melatonin may enhance DNA repair capacity by affecting several key genes involved in DNA damage responsive pathways.
Melatonin (MLT), a hormone secreted by the pineal gland, and plays a crucial role in the regulation of the 24hour circadian rhythm. Melatonin also seems involved in lowering cancer risk by acting as an anti-inflammatory agent and an antioxidant [1,2]. Epidemiologic studies have pointed to an inverse relationship between night shift work and melatonin levels [3], This provides a possible explanation for the observation that female shift workers may have an increased breast cancer risk[4,5]. It has also been shown that a significantly decreased plasma melatonin level imparts a greater risk of endometrial cancer [6,7]. In laboratory studies, functional analysis using cancer cell lines such as MCF-7 have been performed to investigate the effects of melatonin on cell growth, DNA synthesis, cell cycle, and apoptosis [14–17]. These studies have shown that melatonin may reduce MCF-7 cell proliferation by modulating cell-cycle kinetics, DNA synthesis, and apoptotic processes. Other studies have further demonstrated that melatonin can inhibit fatty acid growth-factor uptake [18] and telomerase activity in cancer cells [19]. The role of melatonin in DNA repair pathways was also recently documented in a study that showed a protective role for melatonin against oxidative DNA damage [20].However, the impact of melatonin on DNA repair capacity for DNA strand breaks, the most common type of DNA damage, has not been previously examined using the method used ne in this study- the comet assay. It is a reliable method for detecting and measuring DNA damage and DNA repair capacity [21]. In this study, they performed both a comet assay and genome-wide expression assay using breast cancer cells (MCF-7) and colon cancer cells (HCT-15) to investigate the impact of the body’s melatonin levels on DNA repair capacity and expression of genes in DNA damage response pathways.
To study the impact of melatonin on DNA repair capacity the comet assay was used to assess the differences in DNA damage accumulation, and repair capacity.
Among the samples not treated with a tumorigenic substance, the differences in DNA response pathways between cells in the control group and those in the MLT treatment group were not statistically significant for either cancer cell line studied, indicating that without inducing damage, there is no difference in detected DNA damage levels. However, studying the carcinogen treated cells it was shown that there was an increased DNA repair capacity shown.
To further study the possible mechanisms of the observed protective effect on DNA repair capacity induced by mutagen exposure, they performed a genome-wide expression microarray analysis. There were 104 genes identified from the expression microarray analysis 1. The network most significantly associated with the set of altered genes was defined as having relevance for “DNA Replication, Recombination, and Repair, Gene Expression, [and] Cancer” 2.
The protective role of melatonin in DNA damage that was observed in this study was consistent with previous research reports. Since melatonin was initially identified as a free radical scavenger many years ago, studies have shown that melatonin may protect DNA against free radical damage [27–31] by stimulating antioxidative enzymes and scavenging free radicals [32,33]. Along with stimulating DNA repair capacity, melatonin may aid in inactivating DNA-damaging agents [34]. Prior studies focused their attention on the role of melatonin in protecting the cell against oxidative DNA damage, whereas this study demonstrated that melatonin may also increase DNA repair capacity against strand breaks caused by the DNA damaging agents.
Although increasing evidence suggests a protective role for melatonin in DNA repair pathways, the molecular mechanism is still unclear with regard to the impact of melatonin on the expression of DNA damage response genes. This study examined genome-wide gene expression after induced DNA damage, and it found that melatonin can affect multiple DNA damage responsive pathways associated with repair of DNA damage. [24,34]. [26,35,36]. Melatonin may activate multiple DNA repair processes.
While our data support melatonin’s protective role in DNA strand breaks and suggests potential molecular pathways by which this occurs, without additional experimental evidence, these findings have to be seen as preliminary and not conclusive. Future study needs to be done to provide confirmatory evidence of Melatonin’s effect on DNA repair, and measure the response in specific biological pathways to melatonin induction.
Conclusion
In conclusion this study data does support the hypothesis that melatonin may enhance DNA repair capacity and play a protective role in cancer development. And the data suggests that melatonin may participate in the regulation of several key genes involved in DNA damage repair pathways.
Your brain produces melatonin in response to darkness.
It has been referred to as the “sleep hormone.” It helps with the timing of your circadian rhythms (24-hour internal clock) and with sleep. Being exposed to light at night can block melatonin production. Melatonin can be taken as a supplement to help with sleep problems, such as insomnia or jet lag. The American Academy of Family Physicians (AAFP) recognizes melatonin as the first-line pharmacological therapy for insomnia.
Your pineal gland releases the highest levels of melatonin when there’s darkness and it decreases melatonin production when you’re exposed to light. Thus, you have low levels of melatonin during the daylight hours and peak levels of melatonin during the nighttime. As your pineal gland receives information about the daily light-dark (day-night) cycle from the retina at the back of your eyes it releases melatonin accordingly. You sleep better when you have the highest levels of melatonin in your body.The longer the night, the longer your pineal gland secretes melatonin. People who suffer from blindness who can’t detect light often have irregularly synchronized melatonin cycles leading to circadian rhythm disorders. https://my.clevelandclinic.org/health/articles/23411-melatonin
