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ArticleNaunyn-Schmiedeberg's archives of pharmacology2025

Apoptotic effect of melatonin on ER-positive breast cancer cell lines: ADGRL4 gene expression and promoter methylation.

Ali Rajabi, Reza Safaralizadeh, Ali Saber, Mahsa Pourmahdi, Shahram Teimourian, Vahid Montazeri, Ashraf Fakhrjou, Mohammadali Hosseinpourfeizi

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Article in Naunyn-Schmiedeberg's archives of pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Ali RajabiDepartment of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Reza SafaralizadehDepartment of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran. Safaralizadeh@tabrizu.ac.ir.ORCID 0000-0002-6970-6998
Ali SaberDr. Saber Medical Genetics Laboratory, Almas Complex, Namaz Blvd, Rasht, Gilan, Iran.
Mahsa PourmahdiDepartment of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Shahram TeimourianDepartment of Medical Genetics, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Vahid MontazeriDepartment of Thoracic Surgery, Tabriz University of Medical Sciences, Tabriz, Iran.
Ashraf FakhrjouDepartment of Pathology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Mohammadali HosseinpourfeiziDepartment of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Funding

University of Tabriz TabrizU-300
6 · The paper itself

Abstract

Breast cancer (BC) is the second most common malignancy worldwide. ADGRL4, as a modulator of angiogenesis, undergoes various epigenetic modifications affecting its biological functions. In this study, we aimed to assess ADGRL4 promoter methylation status and its expression levels in primary breast tumors and to evaluate its potency as a plausible prognostic biomarker in BC. Furthermore, we evaluated the effect of melatonin on ADGRL4 expression and viability of BC cells in vitro. One hundred breast tumor tissue samples and adjacent non-tumor tissues were collected, followed by DNA isolation, bisulfite conversion, qRT-PCR, qMSP assay, and immunoblotting. In addition, four BC cell lines were treated with melatonin and subjected to ADGRL4 expression analysis and apoptosis assay. We found a significant correlation between ADGRL4 expression levels and HER2 status and stage of disease (P < 0.05). We observed a substantial attenuation in ADGRL4 promoter methylation in tumor samples compared to marginal non-tumor samples. A significantly lower expression of ADGRL4 was detected in two BC cell lines in the presence of melatonin. MCF-7 and BT474 melatonin-treated cell lines showed a significantly higher number of apoptotic cells than non-treated cells (P < 0.0001). Based on the receiver operating characteristic (ROC) curve analysis, ADGRL4 expression and ADGRL4 promoter methylation status showed moderate prognostic value. We found that melatonin has anti-cancer effects on BC cells. In addition, ADGRL4 expression can potentially be used as a prognostic biomarker in BC.

Indexed as

ApoptosisBreast NeoplasmsDNA MethylationMelatoninAdultBiomarkers, TumorCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsMiddle AgedPromoter Regions, GeneticReceptors, EstrogenBiomarkers, TumorMelatoninReceptors, EstrogenADGRL4Breast cancerMelatoninMethylationPrognostic biomarker

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.