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Melatonin As an Angiogenesis Inhibitor to Combat Cancer: Mechanistic Evidence Publisher Pubmed



Goradel NH1, 2 ; Asghari MH3 ; Moloudizargari M4 ; Negahdari B2 ; Haghiaminjan H5 ; Abdollahi M5, 6
Authors
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Authors Affiliations
  1. 1. Young Researchers and Elite Club, Ardabil Branch, Islamic Azad University, Ardabil, Iran
  2. 2. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
  4. 4. Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran

Source: Toxicology and Applied Pharmacology Published:2017


Abstract

Melatonin, a pineal indolamine, participates in different body functions and is shown to possess diverse biological activities such as anti-tumor action. Angiogenesis inhibition is one of the mechanisms by which melatonin exerts its oncostatic effects. Increased angiogenesis is a major feature of tumor progression, thus angiogenesis inhibition is a critical step in cancer therapy. Melatonin employs a variety of mechanisms to target nutrients and oxygen supply to cancer cells. At the transcriptional level, hypoxia induced factor-1α (HIF-1α) and the genes under its control, such as vascular endothelial growth factor (VEGF) are the main targets of melatonin for inhibition of angiogenesis. Melatonin prevents translocation of HIF-1α into the nucleus thereby hindering VEGF expression and also prevents the formation of HIF-1α, phospho-STAT3 and CBP/p300 complex which is involved in the expression of angiogenesis-related genes. Angiostatic properties of melatonin could be also due to its ability to inhibit VEGFR2's activation and expression. Other angiostatic mechanisms of melatonin include the inhibition of endothelial cell migration, invasion, and tube formation. In the present study, we have reviewed the molecular anti-angiogenesis pathways mediated by melatonin and the responsible mechanisms in various types of cancers both in vitro and in vivo. © 2017 Elsevier Inc.
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