Melatonin's anti-cancer properties are under study

MEDICAL MATTERS

October 07, 2005|By JUDY FOREMAN

Melatonin, long known to insomniac Americans as an over-the-counter sleep aid, is now being studied as a way to prevent and treat breast and other cancers.

Dubbed the "hormone of darkness," melatonin is a hormone that is made by the brain's pineal gland at nighttime. This summer, researchers at Brigham and Women's Hospital in Boston, led by epidemiologist Dr. Eva Schernhammer, showed that women who produced the lowest levels of melatonin had a 70 percent higher chance of getting breast cancer than those with the highest levels.

Schernhammer's group had previously shown that women who work at night are at higher risk of both breast and colon cancer. Light at night can shut off melatonin production.

A Finnish study to be published this fall explores whether women who sleep nine hours or more a night - and hence produce more melatonin - are at lower than average risk of breast cancer.

A co-author of that study, cancer epidemiologist Richard Stevens of the University of Connecticut Health Center in Farmington, said that breast cancer rates are much higher in industrialized countries, where, among other things, people use artificial light at night, which suppresses melatonin production.

"We can't say yet, but the evidence is accumulating that light-at-night, and the consequent decrease in melatonin, may be a major driver of breast cancer," Stevens said.

From an evolutionary point of view, melatonin may have developed as a signal to tell animals when to breed. In sheep, melatonin levels rise in the fall as the nights get longer, and ewes become fertile - perhaps as nature's way of insuring that when they give birth, the weather will be balmier.

Melatonin is also an important regulator of the circadian clock in the brain, which keeps the body on a regular cycle of day and night. Light, whether from the sun or electric lights, suppresses melatonin production. But when light disappears, and darkness falls, there's a cascade of nerve signals from the eye to the pineal gland, which then starts making melatonin.

That's why melatonin has been popularized as a sleep aid. But a government study in 2004 found the melatonin pills on the market had limited effectiveness. A more recent study from MIT suggests that the problem may simply be dosing: The pills that are currently sold in health food stores are many times too strong. A dose of only 0.3 milligrams helps people fall asleep faster, according to a study led by Richard Wurtman, director of MIT's Clinical Research Center.

Frustrated by the high rates of breast cancer in industrialized countries, Stevens hypothesized in the 1980s that light-at-night might drive cancer and that melatonin might protect against it.

"We know that if you take out the pineal gland in animals, that removes all melatonin, and then if you inject cancer cells, the cancer growth rate increases," said Steven Lockley, a neuroscientist at Brigham and Women's, who is now studying blind women to see if they have higher than normal levels of melatonin, and whether they get less breast cancer. "We know that when you put an animal in constant light, that also stops all melatonin production, and you get a similar response. And if you then treat an animal with melatonin, you can slow down the cancer rate."

Researchers are just now starting to look at the treatment potential for melatonin.

At the Bassett Research Institute in Cooperstown, N.Y., Dr. David Blask, a senior research scientist, reported at a cancer meeting this summer that melatonin can "put cancer cells to sleep" by blocking their ability to soak up linoleic acid, which makes cancer cells grow rapidly. In animal studies, Blask said, he has found that cancer cell growth is slower at night, when melatonin is highest, and faster during the day. He also found that adding melatonin to human breast cancer cells grown in rats can slow the cancer's growth.

In other animal studies, Steven Hill, vice chairman of structural and cellular biology at Tulane University in New Orleans, has found that melatonin binds to receptors on both normal and breast cancer cells. Once it lands on a receptor, he said, it acts on chemical signals inside the cell to suppress estrogen, which drives many breast tumors. "We can prevent 85 percent of mammary tumors in our rats with a combination of melatonin and retinoid [vitamin A]," he said.

In Europe, studies of people with cancer who are given melatonin are also promising, though preliminary. Melatonin appears able not only to slow cancer progression and improve survival in advanced cancer patients, but also to protect healthy cells from the side effects of chemotherapy and radiation, said Dr. Fade Mahmoud, a clinical instructor at the University of South Dakota School of Medicine who published a review of the studies this summer.

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