Melatonin as an angiogenesis inhibitor to combat cancer: Mechanistic evidence

Journal Article · Wed Nov 15 04:00:00 EST 2017 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2017.09.022· OSTI ID:22722959

Goradel, Nasser Hashemi ^[1]; Asghari, Mohammad Hossein ^[2]; Moloudizargari, Milad ^[3]; Negahdari, Babak ^[4]; Haghi-Aminjan, Hamed ^[5]; Abdollahi, Mohammad ^[5]

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1. Young Researchers and Elite Club, Ardabil Branch, Islamic Azad University, Ardabil (Iran, Islamic Republic of)
2. Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences, Babol (Iran, Islamic Republic of)
3. Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)
4. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)
5. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

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.

• OSTI ID: 22722959
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 335; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANGIOGENESIS
GROWTH FACTORS
INHIBITION
MELATONIN
NEOPLASMS
PLANT GROWTH