Pathway of deoxynivalenol-induced apoptosis in human colon carcinoma cells

Toxicology. 2009 Oct 1;264(1-2):104-9. doi: 10.1016/j.tox.2009.07.020. Epub 2009 Aug 5.

Abstract

The mycotoxin, deoxynivalenol (DON), is generally detected in cereal grains and grain-based food products worldwide. Therefore, DON has numerous toxicological effects on animals and humans. The present investigation was conducted to determine the molecular aspects of DON toxicity on human colon carcinoma cells (HT 29). To this aim, we have monitored the effects of DON on (i) cell viability, (ii) Heat shock protein expressions as a parameter of protective and adaptive response, (iii) oxidative damage and (iv) cell death signalling pathway. Our results clearly showed that DON treatment inhibits cell proliferation, did not induce Hsp 70 protein expression and reactive oxygen species generation. We have also demonstrated that this toxin induced a DNA fragmentation followed by p53 and caspase-3 activations. Finally, our findings suggested that oxidative damage is not the major contributor to DON toxicity. This mycotoxin induces direct DNA lesions and could be considered by this fact as a genotoxic agent inducing cell death via an apoptotic process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colon / drug effects
  • Colon / pathology*
  • Colonic Neoplasms / pathology*
  • Comet Assay
  • DNA Damage
  • Enzyme Activation / drug effects
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / metabolism
  • Humans
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects
  • Trichothecenes / toxicity*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Trichothecenes
  • Tumor Suppressor Protein p53
  • Caspase 3
  • deoxynivalenol