Antioxidant action via p53-mediated apoptosis

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Biology

Background:

• Antioxidants are typically studied for their effects on radicals.
• Antioxidants can also modulate cellular redox potential.
• The role of redox potential in cellular processes is an emerging area of research.

Purpose of the Study:

• To investigate the effects of different types of antioxidants on cell apoptosis.
• To determine the role of cellular redox potential in antioxidant-induced apoptosis.
• To explore the involvement of the p53 tumor suppressor gene in this process.

Main Methods:

• Treatment of transformed and normal cell lines with sulfur-containing antioxidants (N-acetylcysteine, dimercaptopropanol) and chain-breaking antioxidants (vitamin E).
• Measurement of cellular thiol levels and glutathione levels.
• Analysis of p53 expression and its regulation at the posttranscriptional level.
• Assessment of apoptosis induction in different cell types.

Main Results:

• Sulfur-containing antioxidants induced apoptosis in transformed cells but not normal cells.
• Apoptosis induction was linked to elevated total cellular thiol levels, not increased glutathione.
• Antioxidant-induced apoptosis was dependent on the p53 tumor suppressor gene.
• N-acetylcysteine increased p53 expression by enhancing mRNA translation.

Conclusions:

• Cellular redox potential plays a critical role in antioxidant-induced apoptosis.
• A redox sensor for p53 induction exists, requiring transformation-specific signals for apoptosis.
• Nontoxic antioxidants that manipulate p53-dependent apoptosis show potential for clinical applications.