Melatonin counteracts breast cancer by limiting a gene in breast cancer cells

Breast cancer is one of the most widespread cancer forms, with 80% of cases being classified as estrogen receptor-positive. The risk of this type of breast cancer increases when you receive hormone therapy with estrogen (estradiol). The risk is also increased by hormone-disrupting substances in the environment. However, a new study shows that melatonin is able to inhibit a gene that influences the estrogen receptors in breast cancer cells. Melatonin is primarily known for its role as a sleep hormone, but an increasing amount of research shows cancer-protective potential. It is therefore essential to make enough melatonin yourself or to compensate for deficiencies by taking melatonin supplements.

Cancer stem cells are a challenge in the treatment of cancer, as they may lead to tumor growth, metastases, and resistance towards chemo therapy and antiestrogens such as tamoxifen. It has been known for a long time that melatonin has an effect on the estrogen receptors of the cells, yet the actual mechanism remains unclear. In a new study, however, researchers found that melatonin inhibits a gene (OCT4) that influences estrogen receptors in breast cancer stem cells.
In this study, breast cancer cells were exposed to either estradiol or bisphenol A, both of which stimulate cell growth. Afterwards, the cancer cells were treated with or without melatonin.

Estradiol, bisphenol A, melatonin and their effect on breast cancer cells

Those breast cancer cells that where either exposed to estradiol or bisphenol A significantly increased in number and size, as expected, compared with a group of control cells. However, when the same breast cancer cells were treated with melatonin afterwards, there was a significant reduction of breast cancer cells, and they also decreased in size. Moreover, it turned out that breast cancer cells that were exposed to either estradiol or bisphenol A, and also were exposed to melatonin, reduced more in number and size. The study clearly showed that melatonin had the opposite effect of estradiol and bisphenol A on breast cancer cells. What the scientists had not seen earlier was that melatonin therapy reduces levels of the OCT4 gene in breast cancer cells, thereby also levels of estrogen receptors in the cancer cells, which makes the cells less sensitive to estradiol and bisphenol A.

Melatonin affects all cells in the body

Melatonin is a hormone that controls our 24-hour rhythm, sleep, and many other general physiological processes throughout life. It influences all cells in the body and even functions as a powerful antioxidant that protects cells and repairs cellular damage during our sleep.
Our body’s melatonin secretion is suppressed by daytime light and enhanced at night when it is dark, and it is because of this cycle that we are able to get a good night’s sleep.
Melatonin gets produced by the pineal gland that is situated at the center of the brain. As we grow older, our pineal gland starts to calcify and shrink in size, which results in a lowered production of melatonin. Someone in their 60s have around half the melatonin production as someone in their 20s, and the melatonin output continues to decrease. It is believed that the age-related drop in melatonin levels increases the risk of breast cancer and other cancer types.

Unnatural day-and-night-rhythm (circadian rhythm) and other factors that lower melatonin levels

Over the past decades, the breast cancer rate has increased greatly in the industrialized countries. Some scientists believe that this increase may be caused by the reduced melatonin production that is a result of exposing ourselves to artificial light at night – typically from lamps, computer screens, and other types of displays.
For instance, studies have shown that rats that are exposed to constant light quickly develop cancer in their breast glands. In contrast, breast cancer is less common among blind or visually impaired people.
Night work, stimulants, medicine, jet lag, and radiation from magnetic fields (electrical grids and wireless hardware) may also interfere with the body’s natural melatonin production.

Night work and breast cancer

The Danish Cancer Society has published a study that shows how women who work night shifts are 50% more likely to develop breast cancer, compared with women who have regular day jobs. The explanation is believed to lie in their relative lack of melatonin.

Melatonin’s role in the prevention of breast cancer

Under normal conditions, many years pass from the time the first cell changes appear, until a cancer tumor is detected. Therefore, melatonin’s role in cancer prevention is often underestimated and greater than what one would expect.

Melatonin may also improve follow-up treatment of breast cancer

This is because melatonin suppresses cell growth and enhances the effect of antiestrogens (tamoxifen), which is often associated with side effects and therapy resistance.

References:

Juliana Lopes et al. Melatonin decreases estrogen receptor binding to estrogen response elements sites on the OCT4 gene in human breast cancer stem cells. Genes & Cancer. 2016
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979593/

Elsevier: Sleep hormone help breast cancer drug kill more cancer cells. ScienceDaily 2016

Vinter, Anna Gry, Mogens Helweg Claësson: Melatonins indvirkning på immunsystem og cancer. Ugeskrift for Læger 2015

Kræftens Bekæmpelse

Pierpaoli Walter, Regelson William. The Melatonin Miracle. Simon and Schuster 1996

Pernille Lund: Sund & smuk – hele livet. Ny Videnskab 2016

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