Melatonin for glioblastoma
1.- Latest evidence from the latest scientific papers
¨Melatonin disrupts glioblastoma metabolism and enhances temozolomide cytotoxic effects by chemosensitizing cells. It would allow a reduction in TMZ dosage, therefore decreasing possible side effects and indicating melatonin as a strong therapeutic candidate for glioblastoma therapy¨ Gil, Beatriz Irene Fernandez, et al. "Melatonin Disrupts Glioblastoma Metabolism and Enhances Temozolomide Cytotoxic Effects." Neurosurgery 66.Supplement_1 (2019): nyz310_644.
¨Melatonin inhibits tumorigenicity of glioblastoma stem‐like cells. These results suggested that melatonin attenuated multiple key signals involved in GSC self‐renewal and survival, and further supported melatonin as a promising GBM therapeutic¨ Chen, Xueran, et al. "Melatonin inhibits tumorigenicity of glioblastoma stem‐like cells via the AKT–EZH2–STAT3 signaling axis." Journal of pineal research 61.2 (2016): 208-217.
¨We conclude that the diminishing levels of melatonin have significant debilitating effects on normal physiology and can also be associated with malignant conditions such as glioma¨ Maitra, Sayantan, et al. "Melatonin and its anti-glioma functions: a comprehensive review." Reviews in the neurosciences (2019).
¨Melatonin can have anti-inflammatory, anti-proliferation and anti-apoptotic effects simultaneously with effects on a pathway such as NF-KB. Additionally, there are few side effects reported e. g. sleepiness, but melatonin, along with all the benefits mentioned, has limitations that need to be further investigated so that it can be used as a safe drug in the treatment of glioma¨ Neamati, Foroogh, and Zatollah Asemi. "The effects of melatonin on signaling pathways and molecules involved in glioma." Fundamental & Clinical Pharmacology (2019).
¨Valproate increases melatonin receptors in C6 glioma and increases vitamin D3 chaperones BAG-1 and hsp70 in CNS cells, potentiating vitamin D3 effects. Both are anti-proliferative, with melatonin commonly used in glioma radiotherapy¨ Anderson, George, and Moses Rodriguez. "Valproate and Glioblastoma: Role for Melatonin and Vitamin D3." (2019).
2.- Summary and recommendations
Adverse effects: Despite the fact that melatonin is an unregulated drug in many countries and is often used in excessive doses, there does not appear to be a major pattern of side effects. One report described a search for reports of adverse effects with melatonin over 35 years. Of the nine studies reporting adverse effects, pharmacologic doses were used (1 to 36 mg), and the number of patients was not included. However, headache, confusion, and fragmented sleep were among the side effects reported. Dizziness, somnolence, nausea, and headache have been reported with the melatonin agonist ramelteon.
Several studies have tested the efficacy of melatonin supplementation for slowing tumor progression. One randomized, controlled trial suggested that patients with unresectable brain metastases from solid tumors who were treated with melatonin (20 mg daily by mouth, at 8 PM) experienced a significantly longer survival compared with those receiving supportive care only. However, a second randomized trial in patients with brain metastases did not find any benefit from using melatonin in conjunction with radiation therapy. Lissoni, Paolo, et al. "A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms." Cancer 73.3 (1994): 699-701.
Melatonin has been evaluated in combination with aloe vera, which may have immunomodulating properties. In one report, 50 patients with advanced solid malignancies for whom no effective standard anticancer therapy existed, were treated either with melatonin (920 mg per day) or with melatonin and aloe vera tincture (1 mL twice daily). No response was seen in the former group while two partial responses were observed in the group treated with aloe vera. This result awaits confirmation through a more rigorous trial. Lissoni, Paolo, et al. "Biotherapy with the pineal immunomodulating hormone melatonin versus melatonin plus aloe vera in untreatable advanced solid neoplasms." Natural immunity 16.1 (1998): 27-33.