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Effect of antioxidants on the genotoxicity of phenethyl isothiocyanate

Jared D Hoffman1, William M Ward1, George Loo2

  • 1Department of Nutrition, Cellular and Molecular Nutrition Research Laboratory, University of North Carolina at Greensboro, Greensboro, NC 27412, USA.

Mutagenesis
|February 15, 2015
PubMed

Insights

Plant compounds called isothiocyanates can harm DNA. Certain antioxidants like ascorbic acid (ASC) and trolox (TRX) worsen this DNA damage, while others like N-acetylcysteine (NAC) protect against it, offering potential cancer treatment strategies.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Toxicology

Background:

  • Isothiocyanates (ITCs) are plant-derived compounds with potential chronic disease prevention benefits.
  • However, ITCs can induce genotoxicity by stimulating reactive oxygen species (ROS) production.
  • The role of antioxidants in modulating ITC-induced genotoxicity remains unclear.

Purpose of the Study:

  • To investigate the influence of specific antioxidants on phenethyl isothiocyanate (PEITC)-induced genotoxicity in HCT116 cells.
  • To explore the relationship between PEITC-induced DNA damage, ROS production, and glutathione (GSH) levels.
  • To assess the potential of antioxidants in modifying ITC-induced DNA damage for therapeutic applications.

Main Methods:

  • HCT116 cells were treated with PEITC alone or in combination with antioxidants: N-acetylcysteine (NAC), deferoxamine (DFO), ascorbic acid (ASC), and trolox (TRX).
  • ROS production, DNA damage, and glutathione (GSH) levels were measured.
  • The effect of a GSH synthesis inhibitor, buthionine sulphoxime, was also evaluated.

Main Results:

  • PEITC increased ROS production and lowered GSH levels, causing DNA damage.
  • NAC and DFO attenuated PEITC-induced ROS production, GSH depletion, and DNA damage.
  • ASC and TRX, potent radical scavengers, intensified PEITC-induced DNA damage and did not affect GSH levels, while NAC prevented GSH depletion.
  • Buthionine sulphoxime intensified PEITC-induced DNA damage, suggesting a role for GSH in protection.

Conclusions:

  • Ascorbic acid (ASC) and trolox (TRX) enhance PEITC genotoxicity, potentially by mechanisms independent of direct ROS scavenging or GSH modulation.
  • N-acetylcysteine (NAC) and deferoxamine (DFO) protect against PEITC-induced genotoxicity by mitigating ROS and preserving GSH levels.
  • The findings suggest that certain antioxidants can exacerbate ITC-induced DNA damage, a property that might be harnessed for cancer therapy by inducing apoptosis via DNA damage.

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