Melatonin’s Antineoplastic Potential Against Glioblastoma

Abstract

Glioblastoma (GBM) is one of the most intransigent and aggressive brain tumors, and its treatment is extremely challenging and ineffective. To improve patients’ expectancy and quality of life, new therapeutic approaches were investigated. Melatonin is an endogenous indoleamine with an incredible variety of properties. Due to evidence demonstrating melatonin’s activity against several cancer hallmarks, there is growing interest in its use for preventing and treating cancer. In this review, we report on the potential effects of melatonin, alone or in combination with anticancer drugs, against GBM. We also summarize melatonin targets and/or the intracellular pathways involved. Moreover, we describe melatonin’s epigenetic activity responsible for its antineoplastic effects. To date, there are too few clinical studies (involving a small number of patients) investigating the antineoplastic effects of melatonin against GBM. Nevertheless, these studies described improvement of GBM patients’ quality of life and did not show significant adverse effects. In this review, we also report on studies regarding melatonin-like molecules with the tumor-suppressive properties of melatonin together with implemented pharmacokinetics. Melatonin effects and mechanisms of action against GBM require more research attention due to the unquestionably high potential of this multitasking indoleamine in clinical practice.

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

“…In BC cell lines, treatment with MT decreases tumor aggressiveness and increases apoptosis [ 282 ]. MT plays a number of other different actions as an anti-cancer agent [ 283 ]. Among them, it regulates the expression of estrogen receptors (ER), inhibits enzymes involved in the local synthesis of estrogens, activates the immune system and decreases angiogenesis by downregulating VEGF [ 280 , 284 , 285 , 286 ].…”

Hormonal Regulation of Oligodendrogenesis II: Implications for Myelin Repair

“…Interestingly, melatonin may exert pro-apoptotic effects on cancerous tissues, including oligodendrogliomas [ 190 , 191 , 192 ]. These effects appear to be limited to cancer cells [ 193 ], and melatonin broadly exhibits anti-apoptotic effects on healthy tissues or cells challenged by hypoxia or oxidative stress [ 180 , 194 ].…”

“…Under physiological or oxidative stress conditions, melatonin reduces levels of reactive oxygen species, activates anti-apoptotic signaling factors, and protects mitochondrial function [ 180 , 195 , 196 ]. However, these effects appear to be reversed in glioblastoma, with melatonin inducing reactive oxygen species and interfering with mitochondrial DNA transcription [ 192 , 197 ]; in addition, melatonin applied directly to mitochondria purified from the rat brain induces mitochondrial membrane permeability and mitochondrial release of pro-apoptotic factors and the myelin-associated enzyme, CNPase [ 198 ]. Though CNPase is often used as a marker of myelinating OLs, its contribution to mitochondrial function and its connection to OL survival and axonal maintenance are unclear.…”

Role and Therapeutic Potential of Melatonin in the Central Nervous System and Cancers

“…MLT mitigates the pathogenesis of various types of cancer. Particularly, MLT is involved in preventing the initiation of the tumorigenic pathway and the ability of MLT to retard the progression of cancer [53,181]. Potential ability of antioxidant and immunomodulatory effects of MLT could modulate various gene expression following activation of various transcription factors in CNS cancers, which are likely to be an important mediating event in cancer prevention.…”