High Dose Melatonin

Melatonin is typically thought of as a sleep hormone. However, it plays many other major roles in the body including protecting healthy cells from cancer invasion as well as in high enough doses it has been shown to cause apoptosis of cancer cells in multiple pathways.

Melatonin Research

Jaworek J, Leja-Szpak A. Melatonin influences pancreatic cancerogenesis. Histol Histopathol. 2014 Apr;29(4):423-31. doi: 10.14670/HH-29.10.423. Epub 2013 Nov 21. PMID: 24258787.
Mayo, JC, Hevia, D, Quiros-Gonzalez, I, et al. IGFBP3 and MAPK/ERK signaling mediates melatonin-induced anti-tumor activity in prostate cancer. J Pineal Res. 2017; 62:e12373. https://doi.org/10.1111/jpi.12373
Dun-Xian Tan, Burkhard Pöeggeler, Russel J. Reiter, Li-Dun Chen, Shou Chen, Manchester C. Lucien, Lornell R. Barlow-Walden, The pineal hormone melatonin inhibits DNA-adduct formation induced by the chemical carcinogen safrole in vivo, Cancer Letters, Volume 70, Issues 1–2, 1993, Pages 65-71, ISSN 0304-3835,
https://doi.org/10.1016/0304-3835(93)90076-L.
Sainz, R.M., Mayo, J.C., Tan, D.-x., León, J., Manchester, L. and Reiter, R.J. (2005), Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism. Prostate, 63: 29-43. https://doi.org/10.1002/pros.20155
Gonzalez R, Sanchez A, Ferguson JA, Balmer C, Daniel C, Cohn A, Robinson WA. Melatonin therapy of advanced human malignant melanoma. Melanoma Res. 1991 Nov-Dec;1(4):237-43. doi: 10.1097/00008390-199111000-00003. PMID: 1823632.
Lin YW, Lee LM, Lee WJ, Chu CY, Tan P, Yang YC, Chen WY, Yang SF, Hsiao M, Chien MH. Melatonin inhibits MMP-9 transactivation and renal cell carcinoma metastasis by suppressing Akt-MAPKs pathway and NF-κB DNA-binding activity. J Pineal Res. 2016 Apr;60(3):277-90. doi: 10.1111/jpi.12308. Epub 2016 Feb 3. Erratum in: J Pineal Res. 2017 Jan;62(1): PMID: 26732239.
Roberts, J.E., F. Wiechmann, A. and Hu, D.-N. (2000), Melatonin receptors in human uveal melanocytes and melanoma cells. Journal of Pineal Research, 28: 165-171. https://doi.org/10.1034/j.1600-079X.2001.280306.x
Srinivasan V, Spence DW, Pandi-Perumal SR, Trakht I, Cardinali DP. Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms. Integrative Cancer Therapies. 2008;7(3):189-203. doi:10.1177/1534735408322846
Talib WH, Alsayed AR, Abuawad A, Daoud S, Mahmod AI. Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities. Molecules. 2021; 26(9):2506. https://doi.org/10.3390/molecules26092506
Lissoni P, Bolis S, Brivio F, Fumagalli L. A phase II study of neuroimmunotherapy with subcutaneous low-dose IL-2 plus the pineal hormone melatonin in untreatable advanced hematologic malignancies. Anticancer Research. 2000 May-Jun;20(3B):2103-2105. PMID: 10928160.
Gil-Martín, E, Egea, J, Reiter, RJ, Romero, A. The emergence of melatonin in oncology: Focus on colorectal cancer. Med Res Rev. 2019; 39: 2239-2285. https://doi.org/10.1002/med.21582
Keywan Mortezaee, Masoud Najafi, Bagher Farhood, Amirhossein Ahmadi, Yaiza Potes, Dheyauldeen Shabeeb, Ahmed Eleojo Musa, Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review, Life Sciences, Volume 228, 2019, Pages 228-241, ISSN 0024-3205, https://doi.org/10.1016/j.lfs.2019.05.009.
Lissoni, P., Rovelli, F., Brivio, F., Messina, G., Lissoni, A., Pensato, S., & Di Fede, G. (2018). Five year-survival with high-dose melatonin and other antitumor pineal hormones in advanced cancer patients eligible for the only palliative therapy. Res J Oncol, 2(1), 2.
Liu S, Madu CO, Lu Y. The Role of Melatonin in Cancer Development. Oncomedicine 2018; 3:37-47. doi:10.7150/oncm.25566. http://www.oncm.org/v03p0037.htm