Clinical and Translational Oncology

, Volume 21, Issue 3, pp 268–279 | Cite as

Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization

  • B. Farhood
  • N. H. Goradel
  • K. MortezaeeEmail author
  • N. Khanlarkhani
  • E. Salehi
  • M. S. Nashtaei
  • H. Mirtavoos-mahyari
  • E. Motevaseli
  • D. Shabeeb
  • A. E. Musa
  • M. NajafiEmail author
Review Article


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.


Melatonin Radiotherapy Radioprotection Radiosensitization Inflammation DNA repair Apoptosis Tumor cells metabolism p53 Cancer 


Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Informed consent for this article is not required.


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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.Department of Medical Physics and Radiology, Faculty of Paramedical SciencesKashan University of Medical SciencesKashanIran
  2. 2.Department of Medical Biotechnology, School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
  3. 3.Department of Anatomy, School of MedicineKurdistan University of Medical SciencesSanandajIran
  4. 4.Department of Anatomy, School of MedicineTehran University of Medical SciencesTehranIran
  5. 5.Infertility DepartmentShariati Hospital, Tehran University of Medical SciencesTehranIran
  6. 6.Department of Medical Genetics, Faculty of MedicineTehran University of Medical SciencesTehranIran
  7. 7.Department of Molecular Medicine, School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
  8. 8.Department of Medical Physics and Biomedical Engineering, School of MedicineTehran University of Medical Sciences, International CampusTehranIran
  9. 9.Department of Physiology, College of MedicineUniversity of MisanAmarahIraq
  10. 10.Research Center for Molecular and Cellular Imaging, Tehran University of Medical SciencesTehranIran
  11. 11.Radiology and Nuclear Medicine Department, School of Paramedical SciencesKermanshah University of Medical SciencesKermanshahIran

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