Glyphosate and AMPA-Induced Apoptosis and Epigenetic Alterations in HepG2 Cells: Upregulation of p53-BAX-CASP Pathways

dc.authorscopusid 58077651200
dc.authorscopusid 58091480500
dc.authorscopusid 59963391200
dc.authorscopusid 8951469400
dc.contributor.author Mehtiyev, T.
dc.contributor.author Guler, Z.R.
dc.contributor.author Aktan, E.
dc.contributor.author Ozden, S.
dc.date.accessioned 2025-07-10T20:04:17Z
dc.date.available 2025-07-10T20:04:17Z
dc.date.issued 2025
dc.department Fenerbahçe University en_US
dc.department-temp [Mehtiyev T.] Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey, Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Turkey, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Fenerbahce University, Istanbul, Turkey; [Guler Z.R.] Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey, Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Turkey; [Aktan E.] Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey; [Ozden S.] Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey en_US
dc.description.abstract Glyphosate and its metabolite aminomethylphosphonic acid (AMPA) are environmental contaminants with potential toxic effects. This study aimed to investigate apoptosis and epigenetic alterations induced by glyphosate and AMPA in HepG2 cells. The IC50 values for glyphosate and AMPA were 6.19 mM and 8.13 mM, respectively, following 24 h exposure; mechanistic assays were conducted at sub-cytotoxic concentrations (50–500 μM). Annexin V/PI flow cytometry revealed that AMPA significantly increased early apoptosis (up to 116 %, p < 0.001), while glyphosate elevated late apoptosis (up to 145 %, p < 0.001). Gene expression analysis showed significant upregulation of p53 (≥1.49-fold), BAX (≥1.82-fold), CASP3 (≥1.37-fold), and CASP9 (≥1.83-fold), with no significant change in BCL2. Epigenetic analysis indicated that both glyphosate and AMPA increased global DNA methylation, with fold changes ranging from 1.43 to 1.62-fold at concentrations of 100–250 μM (p < 0.05). DNA methyltransferase genes DNMT1 (≥2.44-fold), DNMT3A (≥1.65-fold), and DNMT3B (≥1.65-fold) were upregulated. Additionally, histone modification profiling showed elevated levels of H3K27me3, H3K9me3, and H3K9ac (p < 0.05), alongside increased expression of G9a (≥1.64-fold), EZH2 (≥2.14-fold), SETD1B (≥2.15-fold), HAT1 (≥2.40-fold), and SIRT1 (≥2.57-fold), and downregulation of SUV39H1 (≥0.27-fold). These findings reveal the molecular mechanisms of glyphosate and AMPA toxicity, linking apoptosis to epigenetic alterations and enhancing understanding of their risks. © 2025 Elsevier Ltd en_US
dc.description.sponsorship Istanbul Üniversitesi, (TDK-2021-37807); Istanbul Üniversitesi en_US
dc.identifier.doi 10.1016/j.fct.2025.115605
dc.identifier.issn 0278-6915
dc.identifier.scopus 2-s2.0-105009135703
dc.identifier.scopusquality Q1
dc.identifier.uri https://doi.org/10.1016/j.fct.2025.115605
dc.identifier.uri https://hdl.handle.net/20.500.14627/1127
dc.identifier.volume 203 en_US
dc.identifier.wosquality Q1
dc.language.iso en en_US
dc.publisher Elsevier Ltd en_US
dc.relation.ispartof Food and Chemical Toxicology en_US
dc.relation.publicationcategory Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı en_US
dc.rights info:eu-repo/semantics/closedAccess en_US
dc.scopus.citedbyCount 0
dc.subject AMPA en_US
dc.subject Apoptosis en_US
dc.subject Dna Methylation en_US
dc.subject Glyphosate en_US
dc.subject HepG2 Cells en_US
dc.subject Histone Modification en_US
dc.title Glyphosate and AMPA-Induced Apoptosis and Epigenetic Alterations in HepG2 Cells: Upregulation of p53-BAX-CASP Pathways en_US
dc.type Article en_US
dspace.entity.type Publication

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