Epigenetic Effects of Melatonin on Breast Cancer Cells in In Vitro Experiment

Background and aim: angiogenesis is an essential process for tumor growth, invasion, and metastasis. as the tumor grows, it eventually develops its own blood vessels to provide a sufficient amount of nutrition and oxygen for the cells. melatonin is a natural compound that secret by the pineal gland and several studies investigated that it has a strong antioxidant effect against free radicals. in this study, we aimed to evaluate the expression of dll4 and adgrl4 in primary breast tumors and to determine the melatonin effect on epigenetic alteration in breast cancer cells in vitro.methods: thirty-two breast tumor and paired adjacent non-tumor tissue samples were collected from the noor-e-nejat hospital, tabriz, iran. we measured the expression of dll4 and adgrl4 by qrt-pcr and western blot. then, we investigated the epigenetic effect of melatonin on the expression of dll4 and adgrl4 in breast cancer cell lines at rna and protein levels and methylation status of the gene's promoter by the msp method.results: our results showed a significantly higher expression of dll4 and adgrl4 in tumor tissues as compared to non-tumor tissues (p=0.027, p=0.0012, respectively). melatonin treatment substantially attenuated dll4 and adgrl4 expression in mcf-7 and bt474 cells, but not in mda-mb-231 and sk-br-3 cells. epigenetic investigations on the melatonin effect in estrogen-responsive breast cancer cell lines revealed dll4 and adgrl4 methylation and therefore their attenuated expression.conclusion: dll4 and adgrl4 were overexpressed in breast cancer tissues as compared to the non-tumor tissues. in addition, melatonin treatment attenuated dll4 and adgrl4 expression only in estrogen-responsive breast cancer cells through methylation induction on their promoters.