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Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization.
Clin Transl Oncol. 2019 Mar; 21(3):268-279.CT

Abstract

It is estimated that more than half of cancer patients undergo radiotherapy during the course of their treatment. Despite its beneficial therapeutic effects on tumor cells, exposure to high doses of ionizing radiation (IR) is associated with several side effects. Although improvements in radiotherapy techniques and instruments could reduce these side effects, there are still important concerns for cancer patients. For several years, scientists have been trying to modulate tumor and normal tissue responses to IR, leading to an increase in therapeutic ratio. So far, several types of radioprotectors and radiosensitizers have been investigated in experimental studies. However, high toxicity of chemical sensitizers or possible tumor protection by radioprotectors creates a doubt for their clinical applications. On the other hand, the protective effects of these radioprotectors or sensitizer effects of radiosensitizers may limit some type of cancers. Hence, the development of some radioprotectors without any protective effect on tumor cells or low toxic radiosensitizers can help improve therapeutic ratio with less side effects. Melatonin as a natural body hormone is a potent antioxidant and anti-inflammatory agent that shows some anti-cancer properties. It is able to neutralize different types of free radicals produced by IR or pro-oxidant enzymes which are activated following exposure to IR and plays a key role in the protection of normal tissues. In addition, melatonin has shown the ability to inhibit long-term changes in inflammatory responses at different levels, thereby ameliorating late side effects of radiotherapy. Fortunately, in contrast to classic antioxidants, some in vitro studies have revealed that melatonin has a potent anti-tumor activity when used alongside irradiation. However, the mechanisms of its radiosensitive effect remain to be elucidated. Studies suggested that the activation of pro-apoptosis gene, such as p53, changes in the metabolism of tumor cells, suppression of DNA repair responses as well as changes in biosynthesis of estrogen in breast cancer cells are involved in this process. In this review, we describe the molecular mechanisms for radioprotection and radiosensitizer effects of melatonin. Furthermore, some other proposed mechanisms that may be involved are presented.

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Authors+Show Affiliations

Farhood B
Department of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran.
Goradel NH
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mortezaee K
Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. mortezaee.k@muk.ac.ir.
Khanlarkhani N
Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Salehi E
Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Nashtaei MS
Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Infertility Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Mirtavoos-Mahyari H
Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Motevaseli E
Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Shabeeb D
Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, International Campus, Tehran, Iran. Department of Physiology, College of Medicine, University of Misan, Amarah, Iraq.
Musa AE
Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, International Campus, Tehran, Iran. Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran.
Najafi M
Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran. najafi_ma@yahoo.com.

MeSH

AnimalsAntioxidantsHumansMelatoninNeoplasmsRadiation InjuriesRadiation ToleranceRadiation-Protective AgentsRadiation-Sensitizing AgentsRadiotherapy

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

30136132

Citation

Farhood, B, et al. "Melatonin as an Adjuvant in Radiotherapy for Radioprotection and Radiosensitization." Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, vol. 21, no. 3, 2019, pp. 268-279.
Farhood B, Goradel NH, Mortezaee K, et al. Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization. Clin Transl Oncol. 2019;21(3):268-279.
Farhood, B., Goradel, N. H., Mortezaee, K., Khanlarkhani, N., Salehi, E., Nashtaei, M. S., Mirtavoos-Mahyari, H., Motevaseli, E., Shabeeb, D., Musa, A. E., & Najafi, M. (2019). Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization. Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 21(3), 268-279. https://doi.org/10.1007/s12094-018-1934-0
Farhood B, et al. Melatonin as an Adjuvant in Radiotherapy for Radioprotection and Radiosensitization. Clin Transl Oncol. 2019;21(3):268-279. PubMed PMID: 30136132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization. AU - Farhood,B, AU - Goradel,N H, AU - Mortezaee,K, AU - Khanlarkhani,N, AU - Salehi,E, AU - Nashtaei,M S, AU - Mirtavoos-Mahyari,H, AU - Motevaseli,E, AU - Shabeeb,D, AU - Musa,A E, AU - Najafi,M, Y1 - 2018/08/22/ PY - 2018/05/13/received PY - 2018/08/02/accepted PY - 2018/8/24/pubmed PY - 2019/5/21/medline PY - 2018/8/24/entrez KW - Apoptosis KW - Cancer KW - DNA repair KW - Inflammation KW - Melatonin KW - Radioprotection KW - Radiosensitization KW - Radiotherapy KW - Tumor cells metabolism KW - p53 SP - 268 EP - 279 JF - Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico JO - Clin Transl Oncol VL - 21 IS - 3 N2 - It is estimated that more than half of cancer patients undergo radiotherapy during the course of their treatment. Despite its beneficial therapeutic effects on tumor cells, exposure to high doses of ionizing radiation (IR) is associated with several side effects. Although improvements in radiotherapy techniques and instruments could reduce these side effects, there are still important concerns for cancer patients. For several years, scientists have been trying to modulate tumor and normal tissue responses to IR, leading to an increase in therapeutic ratio. So far, several types of radioprotectors and radiosensitizers have been investigated in experimental studies. However, high toxicity of chemical sensitizers or possible tumor protection by radioprotectors creates a doubt for their clinical applications. On the other hand, the protective effects of these radioprotectors or sensitizer effects of radiosensitizers may limit some type of cancers. Hence, the development of some radioprotectors without any protective effect on tumor cells or low toxic radiosensitizers can help improve therapeutic ratio with less side effects. Melatonin as a natural body hormone is a potent antioxidant and anti-inflammatory agent that shows some anti-cancer properties. It is able to neutralize different types of free radicals produced by IR or pro-oxidant enzymes which are activated following exposure to IR and plays a key role in the protection of normal tissues. In addition, melatonin has shown the ability to inhibit long-term changes in inflammatory responses at different levels, thereby ameliorating late side effects of radiotherapy. Fortunately, in contrast to classic antioxidants, some in vitro studies have revealed that melatonin has a potent anti-tumor activity when used alongside irradiation. However, the mechanisms of its radiosensitive effect remain to be elucidated. Studies suggested that the activation of pro-apoptosis gene, such as p53, changes in the metabolism of tumor cells, suppression of DNA repair responses as well as changes in biosynthesis of estrogen in breast cancer cells are involved in this process. In this review, we describe the molecular mechanisms for radioprotection and radiosensitizer effects of melatonin. Furthermore, some other proposed mechanisms that may be involved are presented. SN - 1699-3055 UR - https://www.unboundmedicine.com/medline/citation/30136132/Melatonin_as_an_adjuvant_in_radiotherapy_for_radioprotection_and_radiosensitization_ DB - PRIME DP - Unbound Medicine ER -