Dr. Weeks’ Comment: Melatonin, the hormone which is elevated when we sleep deeply, has been shown to help remedy cancer STEM cells – including breast cancer STEM cells. The usual dosage is 3 mg but dosages up to more than 60mg three times a day are commonly used by Corrective Cancer Care doctors.
Melatonin decreases estrogen receptor binding to estrogen response elements sites on the OCT4 gene in human breast cancer stem cells.
Genes Cancer. 2016 May;7(5-6):209-17. doi: 10.18632/genesandcancer.107.
Cancer stem cells (CSCs) pose a challenge in cancer treatment, as these cells can drive tumor growth and are resistant to chemotherapy. Melatonin exerts its oncostatic effects through the estrogen receptor (ER) pathway in cancer cells, however its action in CSCs is unclear.
Here, we evaluated the effect of melatonin on the regulation of the transcription factor OCT4 (Octamer Binding 4) by estrogen receptor alpha (ERÎ±) in breast cancer stem cells (BCSCs). The cells were grown as a cell suspension or as anchorage independent growth, for the mammospheres growth, representing the CSCs population and treated with 10 nM estrogen (E2) or 10 Î¼M of the environmental estrogen Bisphenol A (BPA) and 1 mM of melatonin. At the end, the cell growth as well as OCT4 and ERÎ± expression and the binding activity of ERÎ± to the OCT4 was assessed. The increase in number and size of mammospheres induced by E2 or BPA was reduced by melatonin treatment. Furthermore, binding of the ERÎ± to OCT4 was reduced, accompanied by a reduction of OCT4 and ERÎ± expression. Thus, melatonin treatment is effective against proliferation of BCSCs in vitro and impacts the ER pathway, demonstrating its potential therapeutic use in breast cancer.
Evaluation of melatonin effect on human breast cancer stem cells using a three-dimensional growth method of mammospheres.
Anticancer Agents Med Chem. 2016 Sep 22. [Epub ahead of print]
The high rates of women’s death from breast cancer occur due to acquired resistance by patients to certain treatments, enabling the recurrence and/or tumor growth, invasion and metastasis. It has been demonstrated the presence of cancer stem cells in human tumors, as responsible for recurrence and resistance to therapy. Studies have identified OCT4 as responsible for self-renewal and maintenance of pluripotency of stem cells. Thus, it is interesting to study potential drugs that target this specific population in breast cancer. Melatonin, appears to have oncostatic effects on cancer cells, however, little is known about its therapeutic effect on cancer stem cells.
Our results demonstrated that the melatonin treatment decreased the cell viability of MCF-7 and MDA-MB-231 mammospheres. Furthermore, it was observed that in both cell lines, the expression of OCT4 was decreased in melatonin-treated cells compared to the control group.
This fact suggests that melatonin is effective against breast cancer stem cells inhibiting the cell viability via OCT 4. Based on that, we believe that melatonin has a high potential to be used as an alternative treatment for breast cancer.