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Effects of fumonisin B1 on gene-specific DNA methylation related to cancer pathways of p53 signalling and PI3K/Akt signalling in human kidney cells

In: World Mycotoxin Journal
Authors:
S. Omerustaoglu Bayoglu Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, 34116-Beyazit, Istanbul, Türkiye
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Biruni University, 34015 Topkapi, Istanbul, Turkey

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https://orcid.org/0000-0002-8847-9890
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E.F. Karaman Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Biruni University, 34015 Topkapi, Istanbul, Turkey

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https://orcid.org/0000-0002-1504-4546
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S. Ozden Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, 34116-Beyazit, Istanbul, Türkiye

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https://orcid.org/0000-0002-1662-2504
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Abstract

Fumonisin B1 (FB1), which is emerged by contamination of corn and similar products with Fusarium species, causes a high risk for human and animal health. FB1 shows hepatotoxic, nephrotoxic, neurotoxic, immunotoxic and teratogenic effects. FB1 has also been linked to carcinogenesis processes that are unrelated to genotoxic pathways. Our goal was to investigate the role of gene-specific DNA methylation and expression of tumour suppressor genes in the toxicity of FB1 in human kidney (HK-2) cells. Using array panels, effects of FB1 exposure (10-100 μM) for 24 h on methylation levels of tumour suppressor genes were investigated. ToppGene Suite (Toppfun) portal was used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and Reactome enrichment studies. The most of the genes were hypermethylated significantly at 100 μM concentrations of FB1. These results are consistent with the expression results which downregulate the selected genes of CD44, CDKN1A, CDKN2B, CTNNB1, MYC and p16. Functional enrichment analysis further elucidated the molecular mechanisms of FB1 in cancer-related pathways especially p53 signalling and PI3K/Akt signaling. It has been expected that the present study could contribute to the studies on the mechanisms that play a role in FB1 induced carcinogenesis.

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