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© 2005 American Society for Nutrition J. Nutr. 135:2560-2565, November 2005


Nutrient-Gene Interactions

Garlic Organosulfur Compounds Upregulate the Expression of the {pi} Class of Glutathione S-Transferase in Rat Primary Hepatocytes1

Chia-Wen Tsai, Jaw-Ji Yang*, Haw-Wen Chen, Lee-Yan Sheen{dagger} and Chong-Kuei Lii2

Department of Nutrition, Chung Shan Medical University, Taichung 402, Taiwan; * School of Dentistry, Chung Shan Medical University, Taichung 402, Taiwan; and {dagger} Graduate Institute of Food Science and Technology, National Taiwan University, Taipei 106, Taiwan

2To whom correspondence should be addressed. E-mail: cklii{at}csmu.edu.tw.

The chemopreventive property of garlic is related in part to its induction of phase II detoxification enzymes. In the present study, we investigated the modulatory effect of 3 garlic organosulfur compounds, i.e., diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), which differ in their number of sulfur atoms, on the gene expression of the {pi} class of glutathione S-transferase (GSTP). Hepatocytes isolated from male Sprague-Dawley rats were cultured with 50–200 µmol/L of DAS, DADS, or DATS for 24 h. DADS and DATS increased GST activity toward ethacrynic acid by 40 and 66%, respectively (P < 0.05). Moreover, both garlic allyl sulfides dose dependently induced GSTP mRNA and protein expression. DATS increased the protein level more than DADS (P < 0.05). In contrast, DAS did not affect the activity or the protein or mRNA levels of this phase II drug-metabolizing enzyme. In Clone 9 liver cells, the pTA-luciferase reporter assay showed that luciferase activity in DADS- and DATS-treated cells was 2.8- and 3.9-fold higher than that in control cells, respectively (P < 0.05). Again, luciferase activity was not affected by treatment with DAS. Deletion of –2.7 to –2.6 kb in the GSTP promoter region, which contains the GSTP enhancer (GPE) I element, abolished the upregulation of GSTP transcription by DADS and DATS. Deletion of GPE II, however, did not affect the induction of reporter activity. In conclusion, the effectiveness of 3 garlic allyl sulfides on GSTP expression was related to the number of sulfur atoms in the molecules, and GPE I was responsible for this upregulation.


KEY WORDS: • garlic organosulfur compounds • {pi} class of glutathione S-transferase • gene expression • hepatocytes • rats




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Y.-P. Lei, H.-W. Chen, L.-Y. Sheen, and C.-K. Lii
Diallyl Disulfide and Diallyl Trisulfide Suppress Oxidized LDL-Induced Vascular Cell Adhesion Molecule and E-Selectin Expression through Protein Kinase A- and B-Dependent Signaling Pathways
J. Nutr., June 1, 2008; 138(6): 996 - 1003.
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