Can something as simple as total darkness make tamoxifen more effective?
Tamoxifen is a common hormone therapy drug used by breast cancer patients. It’s classified under a group of drugs called selective estrogen receptor modulators (or SERMs) that bind to estrogen receptors. They prevent estrogen from binding to cancer cells and in turn, prohibit cancer cell growth.
Some medications, when taken together, are stronger than one alone. Augmenting treatment with another medication may help with unwelcome side effects, may allow for the drug to be more readily absorbed in your system, or may tackle a problem area that the other drug does not (as is the case with bisphosphonates and aromatase inhibitors, a cancer treatment duo that rivals tamoxifen that we wrote about here).
Tamoxifen been around for 30 years, but over the past several years, scientists have discovered an important relationship between it and another hormone our bodies produce, melatonin. Melatonin is produced in darkness, and serves a variety of purposes: it helps us sleep, maintains our circadian rhythms, aids in the development of certain bodily tissues, and has been touted as a potential treatment for a variety of ailments (though most either have conflicting results or need far more research).
However, melatonin seems like a promising player in the success of tamoxifen treatment. Here’s why.
Total Darkness Vs. Dim Light
A study spearheaded by a team at Tulane researched the effects of melatonin on tamoxifen in rats implanted with benign, human breast cancer tumors. The rats were divided into groups and lived in one of two environments — 12 hours of light followed by 12 hours of total darkness, or 12 hours of light followed by 12 hours of dim light.
Steven Hill and David Blask, the leaders of Tulane’s Circadian Cancer Biology Group, found that the rats in the 12 hours of light/12 hours of total darkness group experienced normal fluctuations of melatonin: low levels during the light hours, and an increase of melatonin production in total darkness. The rats in the 12 hours of light/12 hours of dim light group, however, had low levels of melatonin throughout both the light and dim light cycle; they didn’t experience an influx of melatonin at all.
They also found that the rats living in the dim light group had 2.6-times the tumor growth as their counterparts who were exposed to total darkness. In fact, the rats living in dim light were completely resistant to tamoxifen when it was given to them, while their counterparts who were given tamoxifen experienced significant tumor regression. However, when the rats in dim light were given a melatonin supplement at night, they, too, experienced tumor regression.
This means that combining tamoxifen and melatonin in a drug could be possible in the future, according to Hill. But there are other factors to consider. “Before this is done we would need to identify the optimal times of day to give the two because if the timing between the two is off, the advantage of giving them in combination may be lost. This brings up another important point: Our levels of melatonin are not determined by sleep, as many people think. It is actually the darkness that is important. During the night, if you sleep in a brightly lit room, your melatonin levels may be inhibited; however, if you are in the dark but cannot sleep, your melatonin levels will rise normally.”
Co-leader Blask added that, “High melatonin levels at night put breast cancer cells to ‘sleep’ by turning off key growth mechanisms. These cells are vulnerable to tamoxifen. But when the lights are on and melatonin is suppressed, breast cancer cells ‘wake up’ and ignore tamoxifen.”
These findings are preliminary, but they suggest that exposure to light at night could seriously inhibit the efficacy of tamoxifen, unless supplemented by melatonin.
However, melatonin isn’t all that stable, so it doesn’t stick around in the body for long and breaks down quickly when it’s injected or taken in pill form. That’s where the scientists at Tabriz stepped in.
Fixing Melatonin’s Short Shelf Life
At Tabriz University of Medical Sciences in Iran, scientists discovered the power of tiny bubbles. In the study — published in Colloids and Surfaces B: Biointerfaces — researcher Dr. Nasser Samadi and his team found that tiny, melatonin-filled bubbles called nanostructured lipid carriers (NLCs) made tamoxifen work even better than it already does.
The melatonin-carrying NLCs skirt around the short shelf life of melatonin by allowing the drug to be released slowly in tiny bubbles — which in turn allows the treatment to kill the cancer cells continually without having to retake the drug.
This could potentially allow for a lower dose of tamoxifen, and in turn, lower the occurrence of unwelcome side effects. Patients who take tamoxifen have an increased risk of uterine cancer, stroke, and pulmonary embolism; they can also experience vision problems, irregular menstruation, hot flashes, and weight loss. Then there’s chemo-resistance, when cancer cells grow accustomed to a treatment and become resistant — eventually making the drug less effective.
Dr. Samadi and his team found that NLCs inhibited cancer cell growth more effectively than melatonin alone. Another promising find was that empty NLCs (without melatonin) didn’t negatively affect the surrounding tissue either. “Lots of nanostructures these days are toxic to the body or to other cells,” Dr. Samadi said, “but we found no significant toxicity in the empty NLCs. The characteristics are very suitable for applying to these kinds of treatments. This research is still at an early stage; the team plans to test their NLCs on other cancer cells and treatments before moving to animal models and, eventually, clinical trials.”
Studies continue to be done about melatonin and tamoxifen. Talk to your doctor about what you can do to get the most out of your cancer treatment.
C. Dixon likes to read, sing, eat, drink, write, and other verbs. She enjoys cavorting around the country to visit loved ones and experience new places, but especially likes to be at home with her husband, son, and dog.