Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells

Abstract

Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators of important signaling pathways. In this context, tumor cells have an altered redox balance compared to normal cells, which can be targeted as an antitumoral therapy by ROS levels and by decreasing the capacity of the antioxidant system, leading to programmed cell death. Melatonin is of particular importance in the development of innovative cancer treatments due to its oncostatic impact and lack of adverse effects. Despite being widely recognized as a pro-oxidant molecule in tumor cells, the mechanism of action of melatonin remains unclear, which has hindered its use in clinical treatments. The current review aims to describe and clarify the proposed mechanism of action of melatonin inducing ROS production in cancer cells in order to propose future anti-neoplastic clinical applications.

Sorafenib versus Lenvatinib Causes Stronger Oxidative Damage to Membrane Lipids in Noncancerous Tissues of the Thyroid, Liver, and Kidney: Effective Protection by Melatonin and Indole-3-Propionic Acid

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Honey: A Promising Therapeutic Supplement for the Prevention and Management of Osteoporosis and Breast Cancer

“…Moreover, quercetin treatment activated apoptosis in MCF-7 cells via the p38MAPK signaling pathway [ 112 ]. Kim et al [ 113 ] detected melatonin and its metabolites in honey, which possess strong free radical scavenging properties [ 114 ]. However, high concentrations of melatonin can induce the production of ROS, leading to apoptosis in a variety of cancers [ 115 , 116 , 117 ].…”

Melatonin regulates cancer migration and stemness and enhances the anti‐tumour effect of cisplatin

“…Melatonin, whose secretion is controlled by circadian rhythms, is a hormone synthesized and secreted mainly by the pineal gland 3 . Many studies have shown that melatonin can effectively inhibit all stages of cancer development and enhance the sensitivity of cancer cells to various anticancer drugs 4–6 . Melatonin is a pleiotropic anticancer molecule that regulates malignant cells via multiple mechanisms, including enhancement of mitochondrial reactive oxygen species, 7 targeting of Wnt/beta‐catenin signalling, 8 regulation of histone modification, 9,10 etc.…”