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Effects of anticarcinogenic monoterpenes on phase II hepatic metabolizing enzymes
J A Elegbede1, T H Maltzman, C E Elson
1Department of Human Oncology, University of Wisconsin-Madison 53792.
Abstract:
The monocyclic monoterpenoid compounds limonene and sobrerol have anticarcinogenic activity when fed during the initiation stage of dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis. Here we investigated the potential roles of hepatic glutathione-S-transferase (GST; EC 2.5.1.18) and uridine diphosphoglucuronosyl transferase (UDPGT; EC 2.4.1.17) in monoterpene-mediated chemoprevention. Diets containing the isoeffective anticarcinogenic terpenes, 5% limonene or 1% sobrerol, elevated hepatic GST activity > 2-fold when measured using the general substrate 1-chloro-2,4-dinitrobenzene and 3,4-dichloronitrobenzene for the GST dimer 3-3. However, there were no significant changes in hepatic GST activity when 1,2-epoxy-3-(p-nitrophenoxy)propane was used. We found that both terpene diets increased GST affinity-purified protein 1.5-fold and the HPLC subunit profile. Liver GST subunit 3 had the greatest increase followed by 1 and 4 with no change in subunit 2. Both terpene diets significantly increased the activity of the methylcholanthrene-inducible and the phenobarbital-inducible UDPGT isozymes. We propose that much of the anticarcinogenic activity of these monocyclic monoterpenes during the initiation phase of DMBA carcinogenesis is mediated through the induction of the hepatic detoxification enzymes GST and UDPGT.
Insights
Limonene and sobrerol, natural compounds, show cancer-preventing effects by boosting liver detoxification enzymes. These monoterpenes enhance glutathione-S-transferase (GST) and uridine diphosphoglucuronosyl transferase (UDPGT) activity, crucial for chemoprevention.
Area of Science:
- Biochemistry
- Chemoprevention
- Toxicology
Background:
- Monocyclic monoterpenoids like limonene and sobrerol exhibit anticarcinogenic properties.
- Their protective effects are observed during the initiation stage of dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in rats.
Purpose of the Study:
- To investigate the role of hepatic glutathione-S-transferase (GST) and uridine diphosphoglucuronosyl transferase (UDPGT) in monoterpene-mediated chemoprevention.
- To understand the molecular mechanisms underlying the anticarcinogenic activity of limonene and sobrerol.
Main Methods:
- Rats were fed diets containing 5% limonene or 1% sobrerol.
- Hepatic GST and UDPGT activities were measured using specific substrates.
- GST protein levels and subunit profiles were analyzed using affinity purification and HPLC.
Main Results:
- Both limonene and sobrerol diets significantly elevated hepatic GST activity (>2-fold) with general substrates.
- GST protein levels increased by 1.5-fold, with notable increases in subunits 3, 1, and 4.
- Activities of methylcholanthrene-inducible and phenobarbital-inducible UDPGT isozymes were significantly increased by both terpene diets.
Conclusions:
- The anticarcinogenic effects of limonene and sobrerol during DMBA carcinogenesis initiation are likely mediated by the induction of hepatic detoxification enzymes GST and UDPGT.
- These findings highlight the potential of dietary monoterpenes as chemopreventive agents.