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Updated: Jun 11, 2025

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Aflatoxin B1 downregulates ARID3 genes to overcome senescence for inducing hepatocellular carcinoma

Dilkash Ara1, Srinivas Dheeravath1, Sathish Kumar Mungamuri1

  • 1Division of Food Safety, Indian Council of Medical Research - National Institute of Nutrition, Jamai-Osmania PO, Hyderabad, 500 007, India.

Toxicon : Official Journal of the International Society on Toxinology
|October 4, 2024
PubMed

Insights

Aflatoxins (AFB1) are food contaminants causing liver damage and cancer. AFB1 overcomes cell senescence by downregulating ARID3A/ARID3B proteins, promoting tumor development.

Area of Science:

  • Hepatology
  • Molecular Oncology
  • Toxicology

Background:

  • Aflatoxins, particularly AFB1, are significant food contaminants linked to liver toxicity and hepatocellular carcinoma.
  • Activated AFB1 forms DNA adducts, triggering cellular checkpoint control mechanisms.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which AFB1 induces hepatocellular carcinoma.
  • To investigate the role of PI3K-Akt signaling and Oncogene-Induced Senescence in AFB1-mediated tumorigenesis.

Main Methods:

  • Investigated AFB1's effects on PI3K-Akt signaling pathways.
  • Analyzed the interplay between DNA checkpoint activation and proliferative signaling.
  • Examined the regulation of ARID3A and ARID3B proteins in response to AFB1 exposure.

Main Results:

  • AFB1 activates PI3K-Akt signaling, crucial for cell survival.
  • Simultaneous activation of DNA checkpoints and proliferative signals induces Oncogene-Induced Senescence.
  • AFB1 downregulates ARID3A and ARID3B, enabling the bypass of senescence and promoting hepatic tumor formation.

Conclusions:

  • AFB1 disrupts cellular protective mechanisms, including senescence, to drive liver cancer.
  • Targeting ARID3A/ARID3B or the senescence pathway may offer therapeutic strategies against aflatoxin-induced liver cancer.

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