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Citrinin Provoke DNA Damage and Cell-Cycle Arrest Related to Chk2 and FANCD2 Checkpoint Proteins in Hepatocellular

Darija Stupin Polančec1, Sonja Homar2, Daniela Jakšić3

  • 1OnkoLab Ltd., 10000 Zagreb, Croatia.

Toxins
|July 26, 2024
PubMed

Insights

Citrinin (CIT), a mycotoxin found in food, damages DNA and causes cell cycle arrest in human cancer cells. This citrinin toxicity is linked to increased DNA repair proteins, impacting cellular health.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Cell Biology

Background:

  • Citrinin (CIT) is a mycotoxin from *Penicillium*, *Aspergillus*, and *Monascus* species.
  • CIT contaminates food and house dust, with known adverse effects on animal organs.
  • The precise mechanisms of CIT toxicity remain incompletely understood.

Purpose of the Study:

  • Investigate the mode of action of CIT on human hepatocellular carcinoma (HepG2) and lung adenocarcinoma (A549) cell lines.
  • Determine the cytotoxic concentrations and genotoxic effects of CIT.
  • Analyze CIT's impact on cell cycle progression and key checkpoint proteins.

Main Methods:

  • MTT proliferation assay to determine cytotoxic concentrations (IC50).
  • Alkaline comet assay for genotoxicity assessment.
  • Flow cytometry for cell cycle analysis.
  • Cell-based ELISA to quantify total and phosphorylated Chk2 and FANCD2 proteins.

Main Results:

  • CIT IC50 values were 107.3 µM for HepG2 and >250 µM for A549 cells, indicating cell-type-dependent sensitivity.
  • Sub-IC50 and near-IC50 concentrations of CIT induced significant DNA damage.
  • CIT exposure led to cell-cycle arrest in the G2/M phase.
  • Increased levels of total and phosphorylated Chk2 and FANCD2 were observed in response to CIT.

Conclusions:

  • Citrinin exhibits cell-type-dependent toxicity.
  • CIT induces genotoxicity and G2/M cell-cycle arrest in human tumor cells.
  • The observed effects are associated with the activation of Chk2 and FANCD2 DNA damage response pathways.
Keywords:
Chk2FANCD2cell-cycle arrestcitrinincytotoxicitygenotoxicityhepatocellular carcinomalung adenocarcinoma

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