Fumonisin Binduces global DNA hypermethylation in human glioblastoma U87MG cells.

in Epigenetics by Ashmika Foolchand, Terisha Ghazi, Anil A Chuturgoon

TLDR

  • Fumonisin B (FB) induces toxicity and carcinogenesis in brain glioblastoma U87MG cells by causing global DNA hypermethylation through increased DNA methyltransferase expressions and DNA demethylase suppression.
  • The study provides new insights into the epigenetic mechanisms of FB-induced toxicity and carcinogenesis.
  • Future research can explore the clinical implications of FB-induced DNA hypermethylation in different cell types and tissues.

Abstract

Fumonisin B(FB) is a common maize contaminant known to induce toxicity and carcinogenesis in humans and animals; however, its epigenetic mechanisms remain poorly understood. DNA methylation is an epigenetic modification that controls gene expression through DNA methyltransferase and demethylase activities. In this study, the effect of FBon DNA methylation in brain glioblastoma U87MG cells was evaluated. FBcytotoxicity was determined by the MTT assay and an ICvalue of 880 µM FBwas obtained. The ELISA-based global DNA methylation assay displayed an increase in 5-methylcytosine levels. qPCR and western blot revealed a significant increase in DNA methyltransferase expressions (DNMT1, DNMT3A, and DNMT3B) and a significant decrease in demethylase expression (MBD2). This data indicates that FBinduces global DNA hypermethylation, through increased DNA methyltransferase expressions and DNA demethylase suppression in U87MG cells, thus suggesting an alternative mechanism of toxicity.

Overview

  • The study investigates the effect of fumonisin B (FB) on DNA methylation in brain glioblastoma U87MG cells.
  • The goal is to understand the epigenetic mechanisms by which FB induces toxicity and carcinogenesis.
  • The study aims to determine the effect of FB on DNA methylation and its downstream consequences on gene expression.

Comparative Analysis & Findings

  • FB was found to be cytotoxic and induce global DNA hypermethylation in U87MG cells.
  • The study showed a significant increase in DNA methyltransferase expressions (DNMT1, DNMT3A, and DNMT3B) and a decrease in demethylase expression (MBD2) upon FB treatment.
  • The ELISA-based global DNA methylation assay displayed an increase in 5-methylcytosine levels, indicating hypermethylation in response to FB.

Implications and Future Directions

  • The study suggests that FB-induced DNA hypermethylation may be an alternative mechanism of toxicity and carcinogenesis.
  • The findings provide valuable insights into the epigenetic mechanisms by which FB induces toxicity and carcinogenesis.
  • Future studies can investigate the role of FB-induced DNA hypermethylation in other cell types and its potential clinical implications.
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