Epigenetic effects of melatonin on breast cancer cells in in vitro experiment

Publish Year: 1399
نوع سند: مقاله کنفرانسی
زبان: English
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CIGS16_216

تاریخ نمایه سازی: 14 اردیبهشت 1400

Abstract:

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 DLL۴ and ADGRL۴ 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 DLL۴ and ADGRL۴ by qRT-PCR and western blot. Then, we investigated the epigenetic effect of melatonin on the expression of DLL۴ and ADGRL۴ 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 DLL۴ and ADGRL۴ in tumor tissues as compared to non-tumor tissues (P=۰.۰۲۷, P=۰.۰۰۱۲, respectively). Melatonin treatment substantially attenuated DLL۴ and ADGRL۴ expression in MCF-۷ and BT۴۷۴ cells, but not in MDA-MB-۲۳۱ and SK-BR-۳ cells. Epigenetic investigations on the melatonin effect in estrogen-responsive breast cancer cell lines revealed DLL۴ and ADGRL۴ methylation and therefore their attenuated expression.Conclusion: DLL۴ and ADGRL۴ were overexpressed in breast cancer tissues as compared to the non-tumor tissues. In addition, melatonin treatment attenuated DLL۴ and ADGRL۴ expression only in estrogen-responsive breast cancer cells through methylation induction on their promoters.

Authors

Ali Rajabi

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

Sepehr Abdolahi

Department of Biology, Faculty of Sciences, Azerbaijan Shahid Madani University, Tabriz, Iran

Farnaz Amini

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

Amir Khodavirdipour

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

Reza Safaralizadeh

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran