The inhibitory effect of melatonin on the proliferation of irradiated A549 cell line.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. The high resistance of this type of cancer to radiotherapy and chemotherapy is the greatest challenge for the complete eradication of cancer cells. Although the combination of chemotherapeutic agents has some promising results, severe side effects may limit the received tumor dose. The current study aimed at evaluating the possible synergic effect of melatonin on radiation-induced apoptosis and cell proliferation inhibition. MATERIALS AND METHODS: A549 cells were incubated with melatonin or vehicle and then irradiated with a single dose of 0, 0.5, 2, or 8 Gy X-rays. The cells were incubated with 1 nM of melatonin or vehicle for 1 week and then treated with 1 mM of melatonin or vehicle 1 h before irradiation. Cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis was assessed using flowcytometry detection of annexin V. RESULTS: Irradiation of the cells with different X-ray doses had no significant impact on MTT results. However, the administration of 1 mM of melatonin 1 h before irradiation significantly reduced the cell proliferation. Nonetheless, there was no significant difference between this treatment group and 1 mM melatonin group. Moreover, the administration of melatonin in combination with irradiation did not show any significant effects on radiation-induced apoptosis. CONCLUSION: The current study results indicated that the treatment of A549 cells with melatonin could suppress cell proliferation, whereas it did not mediate the induction of apoptosis.

Melatonin Ameliorates Radiation-Induced Oxidative Stress at Targeted and Nontargeted Lung Tissue.

PURPOSE: Radiation causes damage to irradiated tissues and also tissues that do not receive direct irradiation through a phenomenon called out-of-field effects. This damage through signals such as inflammatory responses can be transmitted to unirradiated cells/tissues and causes many effects such as oxidative damage. The radioprotective and anti-inflammatory effects of melatonin have been demonstrated in various studies. The aim of this study was to evaluate the effect of pretreatment with melatonin on oxidative damage caused by direct irradiation and out-of-field effects on the lung tissue after pelvic irradiation in rats. MATERIALS AND METHODS: In this experimental study, 42 adult male Wistar albino rats were divided into seven groups (six rats per group) including control, melatonin treatment, localized irradiation to the pelvis (out-of-field group), whole-body scatter group (which gave radiation dose equal to the amount of radiation that the lung had received from the localized pelvic irradiation), direct irradiation to lung, melatonin administration before localized radiation to the pelvis, and melatonin administration before localized radiation to the lung. A 100 mg/kg of melatonin 30 min before irradiation with 5 Gy γ-rays in a local (3.75 cm × 3.75 cm) field to the lower abdomen was administered to the rats, and after 24 h, all rats were sacrificed and their lungs were excised to measure the biochemical parameters including malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD). RESULTS: The results showed that localized irradiation to the lung or pelvis caused an increase in the MDA level. Moreover, pelvis and lung irradiation increased the GPx and SOD activity in the lungs. Pretreatment with melatonin before irradiation reduced the GPx and MDA levels in both targeted and nontargeted lung tissues and reduced the SOD activity after lung irradiation. CONCLUSION: Although pretreatment with melatonin did not increase the activity of SOD and GPx in comparison to the radiation groups, this study showed that preadministration of melatonin can ameliorate the oxidative damage induced by ionizing radiation.