Research Article

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

Volume: 73 Number: 2 April 1, 2026

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

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

Project Number

TDK-2023-39835

References

  1. Ahmadnejad M, Amirizadeh N, Mehrasa R, et al (2017): Elevated expression of DNMT1 is associated with increased expansion and proliferation of hematopoietic stem cells co-cultured with human MSCs. Blood Res, 52, 25.
  2. Alrehaili AA, Gharib AF, Alghamdi SA, et al. (2023): Evaluation of TET family gene expression and 5-hydroxymethylcytosine as potential epigenetic markers in non-small cell lung cancer. In Vivo, 37, 445-453.
  3. Anteneh H, Fang J, Song J (2020): Structural basis for impairment of DNA methylation by the DNMT3A R882H mutation. Nat Commun, 11, 2294.
  4. Bertuzzi T, Giorni P, Rastelli S, et al (2020): Co-occurrence of moniliformin and regulated Fusarium toxins in maize and wheat grown in Italy. Molecules, 25, 2440.
  5. Bioinformatics RCSB. RCSB Protein Data Bank: RCSB PDB; 2025. Available from: https://www.rcsb.org/. (Accessed May 25, 2005).
  6. Broomhead J, Ledoux D, Bermudez A, et al (2002): Chronic effects of moniliformin in broilers and turkeys fed dietary treatments to market age. Avian Dis, 46, 901-908.
  7. Cakir MC, Ozden S (2025): The role of global DNA methylation in citrinin induced toxicity: in vitro and in silico approach. Toxicol Rep, 102046.
  8. Çetin Y, Bullerman LB (2005): Cytotoxicity of Fusarium mycotoxins to mammalian cell cultures as determined by the MTT bioassay. Food Chem Toxicol, 43, 755-764.

Details

Primary Language

English

Subjects

Veterinary Mycology

Journal Section

Research Article

Early Pub Date

December 2, 2025

Publication Date

April 1, 2026

Submission Date

July 2, 2025

Acceptance Date

November 20, 2025

Published in Issue

Year 2026 Volume: 73 Number: 2

APA
Ciftci, Z., Güler, Z. R., Çakır, M. C., & Özden, S. (2026). In vitro and in silico insights into moniliformin induced global DNA methylation in liver cells. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 73(2), 127-136. https://doi.org/10.33988/auvfd.1732585
AMA
1.Ciftci Z, Güler ZR, Çakır MC, Özden S. In vitro and in silico insights into moniliformin induced global DNA methylation in liver cells. Ankara Univ Vet Fak Derg. 2026;73(2):127-136. doi:10.33988/auvfd.1732585
Chicago
Ciftci, Zeynep, Zeynep Rana Güler, Metin Caner Çakır, and Sibel Özden. 2026. “In Vitro and in Silico Insights into Moniliformin Induced Global DNA Methylation in Liver Cells”. Ankara Üniversitesi Veteriner Fakültesi Dergisi 73 (2): 127-36. https://doi.org/10.33988/auvfd.1732585.
EndNote
Ciftci Z, Güler ZR, Çakır MC, Özden S (April 1, 2026) In vitro and in silico insights into moniliformin induced global DNA methylation in liver cells. Ankara Üniversitesi Veteriner Fakültesi Dergisi 73 2 127–136.
IEEE
[1]Z. Ciftci, Z. R. Güler, M. C. Çakır, and S. Özden, “In vitro and in silico insights into moniliformin induced global DNA methylation in liver cells”, Ankara Univ Vet Fak Derg, vol. 73, no. 2, pp. 127–136, Apr. 2026, doi: 10.33988/auvfd.1732585.
ISNAD
Ciftci, Zeynep - Güler, Zeynep Rana - Çakır, Metin Caner - Özden, Sibel. “In Vitro and in Silico Insights into Moniliformin Induced Global DNA Methylation in Liver Cells”. Ankara Üniversitesi Veteriner Fakültesi Dergisi 73/2 (April 1, 2026): 127-136. https://doi.org/10.33988/auvfd.1732585.
JAMA
1.Ciftci Z, Güler ZR, Çakır MC, Özden S. In vitro and in silico insights into moniliformin induced global DNA methylation in liver cells. Ankara Univ Vet Fak Derg. 2026;73:127–136.
MLA
Ciftci, Zeynep, et al. “In Vitro and in Silico Insights into Moniliformin Induced Global DNA Methylation in Liver Cells”. Ankara Üniversitesi Veteriner Fakültesi Dergisi, vol. 73, no. 2, Apr. 2026, pp. 127-36, doi:10.33988/auvfd.1732585.
Vancouver
1.Zeynep Ciftci, Zeynep Rana Güler, Metin Caner Çakır, Sibel Özden. In vitro and in silico insights into moniliformin induced global DNA methylation in liver cells. Ankara Univ Vet Fak Derg. 2026 Apr. 1;73(2):127-36. doi:10.33988/auvfd.1732585