Apoptotic effect of melatonin on ER-positive breast cancer cell lines: ADGRL4 gene expression and promoter
Ali Rajabi1, Reza Safaralizadeh2, Ali Saber3
1Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
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.
Insights
ADGRL4 expression and promoter methylation show potential as breast cancer (BC) prognostic biomarkers. Melatonin demonstrates anti-cancer effects, reducing BC cell viability and increasing apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Breast cancer (BC) is a leading global malignancy.
- ADGRL4, an angiogenesis modulator, is subject to epigenetic changes impacting its function.
- Investigating ADGRL4's role in BC prognosis and response to melatonin is crucial.
Purpose of the Study:
- To evaluate ADGRL4 promoter methylation and expression in breast tumors.
- To assess ADGRL4 as a prognostic biomarker for BC.
- To determine melatonin's effect on BC cell viability and ADGRL4 expression.
Main Methods:
- Analysis of 100 breast tumor and adjacent non-tumor tissues.
- DNA isolation, bisulfite conversion, qRT-PCR, qMSP, and immunoblotting were performed.
- In vitro studies involved treating BC cell lines with melatonin, followed by expression analysis and apoptosis assays.
Main Results:
- ADGRL4 expression correlated significantly with HER2 status and disease stage.
- Tumor samples showed reduced ADGRL4 promoter methylation compared to non-tumor samples.
- Melatonin decreased ADGRL4 expression and increased apoptosis in BC cell lines (MCF-7, BT474).
Conclusions:
- ADGRL4 expression and promoter methylation offer moderate prognostic value in breast cancer.
- Melatonin exhibits anti-cancer properties against BC cells.
- ADGRL4 is a potential prognostic biomarker for breast cancer.
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