DNA and protein methyltransferases inhibition by adenosine dialdehyde reduces the proliferation and migration of breast and lung cancer cells by downregulating autophagy

Sep 24, 2026

Protein and DNA methylation participate in signaling, DNA repair, and gene expression, while dysregulated methyltransferases are associated with cancer. The study explores how methyltransferase inhibition relates to autophagy and carcinogenesis in breast and lung cancer. Using UALCAN and TCGA datasets, it identifies 17 upregulated methyltransferases and evaluates AdOx in breast (MDA-MB-231, MCF-7) and lung (H292, A549) cell lines. AdOx reduces migration and growth and suppresses autophagy markers ATG7, LC3-II/LC3-I, and increases p62, suggesting a treatment target.

LanguageEnglish

CategoryHealthcare

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Pages14

Reading Time35 min

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Abstract

Introduction

Epigenetic regulation and methylation in cancer

Abbreviations

PLOS ONE OPEN ACCESS Citation: Ghemrawi R, Al Qassem A, Ramadan A, Aldulaymi R, Sammani N, K. Mousa W, et al.(2023) DNA and protein methyltransferases inhibition by adenosine dialdehyde reduces the proliferation and migration of breast and lung cancer cells by downregulating autophagy. PLoSONE 18(7): e0288791 . [https://doi.org/10.1371/](https://doi.org/10.1371/)[ ](https://doi.org/10.1371/)[journal.pone.0288791](journal.pone.0288791) Editor: Vinod Vijayakurup, University of Florida, UNITED STATES Received: April 12, 2023 Accepted: July 3, 2023 Published: July 28, 2023 Copyright: © 2023 Ghemrawi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All data and materials supporting the findings of this study are included in the manuscript. Funding: The present study was supported by Al Ain University, United Arab Emirates, grant number Ph2021-2-905. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. RESEARCH ARTICLE DNA and protein methyltransferases inhibition by adenosine dialdehyde reduces the proliferation and migration of breast and lung cancer cells by downregulating autophagy Rose Ghemrawi1,2☯*, Aya Al Qassem1,2☯, Azza Ramadan1,2, Raghad Aldulaymi2, Nour Sammani1,2, Walaa K. Mousa1,2,3, Mostafa Khair4 1 College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates, 2 AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, United Arab Emirates, 3 College of Pharmacy, Mansoura University, Mansoura, Egypt, 4 Core Technology Platforms, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates ☯ These authors contributed equally to this work. * [rose.ghemrawi@aau.ac.ae](rose.ghemrawi@aau.ac.ae) Abstract Protein and DNA methylation is involved in various biological functions such as signal transmission, DNA repair, and gene expression. Abnormal regulation of methyltransferases has been linked to multiple types of cancer, but its link to autophagy and carcinogenesis in breast and lung cancer is not fully understood. We utilized UALCAN, a web tool, to investigate breast and lung cancer database from The Cancer Genome Atlas. We found that 17 methyltransferases are upregulated in breast and/or lung cancer. We investigated the effect of methylation inhibition on two breast cancer cell lines (MDA-MB-231 and MCF-7) and two lung cancer cell lines (H292 and A549) by treating them with the indirect methyltransferase inhibitor adenosine dialdehyde (AdOx) . We found that the migration ability of all cell lines was decreased, and the growth rate of MDA-MB-231, MCF-7 and H292 was also decreased after AdOx treatment. These results were correlated with an inhibition of the autophagy in MDA-MB-231, MCF-7 and H292 cell lines, since AdOx treatment induced a decreased expression of ATG7, a reduced ratio LC3-II/LC3-I and an increased p62 level. These findings suggest that inhibiting cells’ methylation ability could be a potential target for breast and lung cancer treatment. Introduction Changes in genes can control the growth and spread of cancer, however, scientists have also recognized the significance of epigenetic regulation in the development of cancer. The importance of histone and DNA methylation in tumorigenesis has been well recognized [ 1] . For instance, research has linked cancer to overexpression of DNA methyltransferases (DNMTs) Competing interests: The authors have declared that no competing interests exist. Abbreviations: 53BP1, p53-binding protein 1; AdOx, Adenosine dialdehyde; AP-1, Activator protein-1; ATM, Ataxia telangiectasia mutated gene; BRCA, Breast invasive carcinoma; BRCA1, Breast cancer type 1 susceptibility protein; DAL-1, Differentially expressed in adenoca

FAQs

What dataset and tool were used to analyze methyltransferase expression in breast and lung cancer?

The study used UALCAN to investigate breast and lung cancer databases from The Cancer Genome Atlas (TCGA).

Which inhibitor was tested to block methyltransferase activity in cancer cell lines?

Adenosine dialdehyde (AdOx), described as an indirect methyltransferase inhibitor, was used for cell treatments.

How did AdOx affect cancer cell proliferation, migration, and autophagy-related markers?

AdOx decreased migration in all tested cell lines and reduced growth in MDA-MB-231, MCF-7, and H292. It also inhibited autophagy, shown by reduced ATG7 expression, a lower LC3-II/LC3-I ratio, and increased p62 levels.

Sep 24, 2026

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