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Effects of glutathione on antioxidant response element-mediated gene expression and apoptosis elicited by

Bok-Ryang Kim1, Rong Hu, Young-Sam Keum

  • 1Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854, USA.

Cancer Research
|November 13, 2003
PubMed

Insights

Reduced glutathione (GSH) plays a key role in sulforaphane (SFN)-induced gene expression and apoptosis. Adding GSH blocks SFN

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Sulforaphane (SFN) and its N-acetyl-L-cysteine (NAC) conjugate inhibit tumorigenesis by inducing antioxidant response element (ARE)-related genes and apoptosis.
  • Reduced glutathione (GSH) is crucial for cellular defense mechanisms and redox homeostasis.

Purpose of the Study:

  • To investigate the role of GSH in SFN- and SFN-NAC-induced ARE-mediated gene expression, apoptosis, and c-Jun NH(2)-terminal kinase (JNK) activation in HepG2-C8 cells.
  • To elucidate the differential effects of SFN and SFN-NAC on these cellular processes and the influence of extracellular GSH.

Main Methods:

  • HepG2-C8 cells were treated with varying concentrations of SFN and SFN-NAC.
  • Cellular GSH levels, ARE-mediated gene expression, caspase 3 activity, and JNK1/2 activation were measured.
  • Cells were pretreated with L-buthionine sulfoximine or supplemented with extracellular GSH to assess GSH's role.

Main Results:

  • SFN caused a transient decrease followed by a significant increase in cellular GSH levels, while SFN-NAC had minimal impact.
  • SFN induced ARE expression more potently than SFN-NAC, an effect enhanced by L-buthionine sulfoximine.
  • Extracellular GSH addition blocked SFN-induced ARE expression and JNK1/2 activation, and reduced SFN-induced apoptosis.
  • Higher concentrations of SFN and SFN-NAC correlated with increased apoptosis and caspase 3 activation.

Conclusions:

  • SFN and SFN-NAC exhibit distinct mechanisms in modulating ARE-related gene expression and apoptosis.
  • Cellular GSH levels are critical for mediating the biological effects of SFN.
  • The pro-apoptotic and gene-regulatory effects of SFN are significantly influenced and can be inhibited by GSH.

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