Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization

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.

Biochemical and Histopathological Evaluation of the Radioprotective Effects of Melatonin Against Gamma Ray-Induced Skin Damage

“…Because it has the ability to neutralize free radicals, upregulate antioxidant enzymes and defeat pro-oxidant enzymes. Melatonin is a potent stimulator of DNA repair [69]. Our results are in agreement with another study which revealed that melatonin can inhibit dermatitis in breast cancer radiotherapy [70].…”

The role of melatonin in colorectal cancer treatment: a comprehensive review

“…Melatonin (MLT), a natural body hormone, previously demonstrated impressive protective properties against toxic effects of CTx and radiotherapy, in both experimental and clinical studies. 13 – 15 This could pave the way for application of higher doses of CTx, resulting in improved efficacy. 16 Moreover, MLT itself exerts antiproliferative, antimetastatic, and cytotoxic effects on different types of human malignancies, including CRC.…”

Therapeutic effects of kaempferol affecting autophagy and endoplasmic reticulum stress

“…The history of traditional herb medicine dates back to a long time ago, however, during the recent decades owing to the considerable positive impacts of herbals (Aliasgharzadeh et al, ; Farhood et al, ; Mortezaee et al, ; Najafi et al, ; Shabeeb et al, ) and noticeable side effects of chemical drugs, much attention has been made in pharmacognosy (Farhood et al, , , , ; Najafi et al, ). In other words, the harmful effects of synthetic drugs lead to the substitution of natural compounds for the remediation of a number of disorders (Azmoonfar et al, ; Farhood et al, ; Kolivand et al, ; Shabeeb et al, ).…”