Melatonin May Reduce Tumor Growth and Metastases



What is melatonin?

WebMDart cherries, plums, red wine, pineapple, oranges, bananas, mustard, tomatoes, walnut, sweet corn, rolled oats, and red, black, or purple riceeduced by cool light colors. Melatonin is increased by red light and r for more on this. It is naturally occurring in many foods such as sour or t such as green and blue. Red meat also reduces it. Melatonin is a hormone produced by the pineal gland that helps regulate the circadian rhythm, mood,sleep, and even aging. It is a useful sleep aid, despite limited evidence, and may improve quality of life in cancer patients. Please see the article form the October 25 issue of ASCO Post by Dr. Bao, et al. It also helps treat seasonal affective disorder, sleep patterns for people working night shifts, anxiety, surgical pain, and the frequency of migraine and cluster headaches.

Melatonin and Breast Cancer

While there are quite a few studies on receptor positive breast cancer, there is little on patients with TNBC. Opera-llies, et al. found that melatonin receptor (MT1) was expressed in about 49% of TNBC tumors of caucasian women and 12% in African American women. Younger women and those with a family history of breast cancer tended to have less expression of the MT1 receptor. Presence of the receptor significantly correlated with progression free survival and overall survival in women over 50. Out of the 167 patients, there were not enough women under 50 to find significance. In this small study, the presence of the receptor correlated with the size of tumor at diagnosis as well as the stage. In 2016, Maschi-Signorini et. al. from São José do Rio Preto found that melatonin regulates angiogenic and inflammatory proteins, which contribute to tumor progression in the MDA-MB-231 TNBC cancer line in the laboratory. Melatonin also did this in the presence of cancer associated fibroblasts, which increase tumor malignancy. Bruna Victorasso Jardim-Perassi et. al. in PLoS One (2014) injected a PHARMACOLOGIC dose of melatonin (40mg/kg) into the peritoneum (abdomen) of 5 mice who had xenografts of cultured MDA-MB-231 cells for five days a week over a period of 21 days. On day 22, they evaluated tumor size, VEGFR expression, EGFR, and IGF-I, Ki-67 as well as the expression of other membrane proteins. Mean tumor volume of treated mice was 145 mm3 compared to 282 mm3 in non-treated mice. In one mouse, there was tumor regression. EGFR and IGF-I expression increased while Ki-67 and VEGF2R expression was significantly decreased in the treated group. Micro-vessel density was also reduced by melatonin.

My take

Melatonin in pharmacological concentrations (such as the 1mM concentration used in the study) is probably safe. Unfortunately, the mice received, by intraperitoneal injection, 40 mg/kg of melatonin. The physiologic amount recommended for humans orally is usually on the order of 200 micrograms to about 5 mg at night. Such low concentrations evaluated in the study did not have a significant impact. I still use melatonin as a sleep aid and have been very impressed with the efficacy so far. However, we need much more evidence to suggest that this could be used as part of treatment for TNBC. Physiologic concentrations appeared to work better in receptor positive patients but the role of melatonin with aromatase inhibitors needs to be further defined as studies are conflicting. Always discuss any medications with your oncologist. I like the summary of articles provided by Breast Cancer Choices. Also, not all melatonin is equal. I have experienced some brands that work and others that do not. My current favorite is the CVS brand chewables pictured above.

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