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Induction of phase II enzyme activity by various selenium compounds
1Department of Food Science, University of Wisconsin-Madison, WI 53706, USA.
Nutrition and Cancer
|October 19, 2006
Summary
Certain selenium compounds can significantly boost quinone reductase (QR) and glutathione-S-transferase (GST) enzyme activity in liver cells. The most potent compounds showed this effect at very low concentrations, suggesting a common mechanism of action.
Area of Science:
- Biochemistry
- Toxicology
- Medicinal Chemistry
Background:
- Enzyme induction plays a crucial role in cellular defense mechanisms against xenobiotics.
- Quinone reductase (QR) and glutathione-S-transferase (GST) are key enzymes involved in detoxification pathways.
- Organoselenium compounds are known for their diverse biological activities, including potential roles in cancer chemoprevention.
Purpose of the Study:
- To investigate the potential of various selenium and organosulfur compounds to induce quinone reductase (QR) and glutathione-S-transferase (GST) activity.
- To identify the most potent selenium compounds for QR and GST induction in a murine hepatoma cell line.
- To explore the relationship between the chemical structure of organoselenium compounds and their enzyme-inducing effects.
Main Methods:
- Hepa 1c1c7 murine hepatoma cells were treated with 27 selenium compounds and 16 organosulfur compounds.
- Enzyme-inducing activity was assessed by measuring the specific activity of quinone reductase (QR) and glutathione-S-transferase (GST).
- Dose-response relationships for QR induction and cell growth inhibition were analyzed for potent compounds.
Main Results:
- Sixteen out of 27 tested selenium compounds demonstrated the ability to double QR activity.
- Seven of these selenium compounds also exhibited the capacity to double GST activity.
- Nine potent selenium compounds, including ebselen, induced QR activity at concentrations below 7 microM.
- A strong linear correlation was observed between QR induction and cell growth inhibition for organoselenium compounds with selenol-generating potential.
Conclusions:
- Organoselenium compounds are effective inducers of QR and GST activity in Hepa 1c1c7 cells.
- The enzyme-inducing and cytotoxic effects of certain organoselenium compounds are likely mediated by their selenol metabolites.
- These findings highlight the potential of specific selenium compounds as modulators of detoxification enzymes.
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