Sleep Hormone Melatonin Use in Breast Cancer Treatment

The hormone melatonin can be used in the treatment of breast cancer as it promotes cell death and reduces tumor aggressiveness and metastasis.

A group of genes regulated by the hormone melatonin in some types of cancer, especially in breast cancer, can be used to guide future personalized therapies.

The Brazilian study published in the Journal of Pineal Research was conducted in collaboration with researchers at the São José do Rio Preto Medical School (FAMERP) and University of North Paraná (UENP) in Brazil and the University of Texas Health Science Center at San Antonio in the United States.

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‘Melatonin can be used in the treatment of breast cancer as it promotes cell death and reduces tumor aggressiveness and metastasis.’
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Luiz Gustavo Chuffa professor at São Paulo State University’s Botucatu Institute of Biosciences (IBB-UNESP) said, “Certain types of tumor appear to correlate directly with the amount of melatonin produced by cells. It’s essential to understand how the hormone influences molecular signaling at the genetic level as a guideline for personalized therapies based on melatonin.”

Melatonin is known as the sleep hormone and it regulates the sleep-wake cycle. Laboratory trials show that it also has anti-tumor properties. According to the evidence in the scientific literature, low levels melatonin can increase cancer risk. A possible explanation for this is that the hormone contributes to modulation of gene expression and it can also intensify the activity of tumor suppressor genes.

Chuffa said, “Most tumor cells have low levels of melatonin, but laboratory trials have shown that treatment with the hormone increases tumor cell death and reduces tumor cell proliferation, both of which are important to avoid progression of the cancer and metastasis. Ongoing clinical trials are evaluating the use of melatonin to treat cancer. Specific therapies for the different subtypes of breast cancer already exist, and some patients will probably respond well to alternative treatments based on melatonin, while others may not.”

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Search for Target Genes

A study was conducted to identify molecular markers that can serve as guides for cancer treatment. A meta-analysis was conducted to find out how melatonin regulates microRNA expression in liver, stomach, prostate, breast, head and neck, central nervous system, and colorectal cancer.

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MicroRNAs are small RNA molecules which perform regulatory function on genome by controlling gene expression and hence several cellular processes.

Using bioinformatics, the researchers identified the pathway related to the hormone’s action on the tumor cells. The researchers based their analysis on the relation between the microRNAs and the regulatory targets.

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Chuffa said, “When we cross-referenced the information with The Cancer Genome Atlas (TCGA), a public database, we identified the target genes for these 46 microRNAs with altered expression. These genes targeted by melatonin relate to important biological processes in cancer, such as cell cycle regulation, cell death, and cell migration and senescence. Melatonin appears to act more strongly on breast, oral, and stomach cancer. Prostate and colorectal tumors, as well as glioblastoma, showed few changes induced by the microRNAs concerned.”

In the first stage of the study, it was found that breast cancer was associated with most of the genes and microRNAs. The researchers compared the target genes for microRNA from analysis of breast tumors in mice treated with melatonin which was obtained by a technique called RNA-seq.

RNA-seq is a next-generation sequencing technology that studies the expression of several genes at the same time to obtain the complete set of RNA molecules expressed in a tissue.

The researchers found that in animals who were treated with 40 milligrams of melatonin, there was an increase in the signaling pathways related to the immune system and cell death, and a reduction in pathways related to tumor aggressiveness and metastasis. The researchers also studied certain proteins like transcription factors and kinases which are active in transcription and cell cycle.

The genes which are regulated by melatonin in breast cancer are the potential targets for the treatments. Chuffa said, “Melatonin is a multitasking molecule and acts on various cellular substrates, so we’re now taking the study deeper to find out how the hormone influences microRNA expression and hence the regulation of the cellular mechanisms identified.”

Source-Medindia