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Therapeutic Targets of Cancer Drugs: Modulation by Melatonin Publisher Pubmed



Moloudizargari M1 ; Moradkhani F2 ; Hekmatirad S3 ; Fallah M4 ; Asghari MH5 ; Reiter RJ6
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Department of Medical Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pharmacology and Toxicology, School of Medicine, Student Research Committee, Babol University of Medical Sciences, Babol, Iran
  4. 4. Medicinal Plant Research Centre, Faculty of Pharmacy, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
  5. 5. Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
  6. 6. Department of Cell Systems and Anatomy, Long School of Medicine, UT Health, San Antonio, TX, United States

Source: Life Sciences Published:2021


Abstract

The biological functions of melatonin range beyond the regulation of the circadian rhythm. With regard to cancer, melatonin's potential to suppress cancer initiation, progression, angiogenesis and metastasis as well as sensitizing malignant cells to conventional chemo- and radiotherapy are among its most interesting effects. The targets at which melatonin initiates its anti-cancer effects are in common with those of a majority of existing anti-cancer agents, giving rise to the notion that this molecule is a pleiotropic agent sharing many features with other antineoplastic drugs in terms of their mechanisms of action. Among these common mechanisms of action are the regulation of several major intracellular pathways including mitogen-activated protein kinase (MAPK), extracellular signal–regulated kinase (ERK) and protein kinase B (AKT/PKB) signaling. The important mediators affected by melatonin include cyclins, nuclear factor-κB (NF-κB), heat shock proteins (HSPs) and c-Myc, all of which can serve as potential targets for cancer drugs. Melatonin also exerts some of its anti-cancer effects via inducing epigenetic modifications, DNA damage and mitochondrial disruption in malignant cells. The regulation of these mediators by melatonin mitigates tumor growth and invasiveness via modulating their downstream responsive genes, housekeeping enzymes, telomerase reverse transcriptase, apoptotic gene expression, angiogenic factors and structural proteins involved in metastasis. Increasing our knowledge on how melatonin affects its target sites will help find ways of exploiting the beneficial effects of this ubiquitously-acting molecule in cancer therapy. Acknowledging this, here we reviewed the most studied target pathways attributed to the anti-cancer effects of melatonin, highlighting their therapeutic potential. © 2020 Elsevier Inc.
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