In vitro and in silico insights into moniliformin induced global DNA methylation in liver cells

Year 2025, Issue: Advanced Online Publication, 1 - 10

Zeynep Ciftci , Zeynep Rana Güler , Metin Caner Çakır , Sibel Özden

https://doi.org/10.33988/auvfd.1732585

Abstract

Moniliformin (MON) is a mycotoxin that is not routinely monitored in foods; however, it is increasingly recognized as an emerging food safety concern. Although some clastogenic effects were observed, non-genotoxic mechanisms may also contribute to the toxic effects of MON. Therefore, this study aims to investigate the effects of global DNA methylation, the most studied non-genotoxic mechanism, on MON toxicity in human hepatocarcinoma (HepG2) cells. HepG2 cells were exposed to MON at 5, 10, and 50 M concentrations for 24 hours. Global DNA methylation levels and gene expression of DNMT1, DNMT3A, DNMT3B, TET1, TET2, and TET3 were analyzed. Interactions among B-DNA, DNMT1, DNMT3A, DNMT3B, and MON were investigated using molecular docking. MTT cytotoxicity assay revealed that the IC50 value of MON in HepG2 cells was 253±8.41 M. MON at 10 and 50 μM resulted in at least a 2.18-fold increase (P<0.05) in global DNA methylation levels, accompanied by upregulated expression of DNMT1 and DNMT3A. Moreover, 5, 10, and 50 M of MON resulted in at least 2.37-fold (P<0.05) increase in TET1 genes. In contrast, TET2 expression was significantly downregulated by at least 37% (P<0.05) and 42% (P<0.05) at 10 and 50 M of MON. However, TET3 expression showed no significant change in any treatment group. MON formed hydrogen bonds with B-DNA, DNMT1, DNMT3A, and DNMT3B. However, the binding energy calculations indicate that the interactions are not biologically active. This study suggests that alterations in global DNA methylation might have a role in MON-induced toxicity.

Keywords

Epigenetics , Global DNA methylation , HepG2 cells , Molecular docking , Moniliformin

Project Number

TDK-2023-39835

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