Garlic organosulfur compounds upregulate the expression of the pi class of glutathione S-transferase in rat primary hepatocytes.
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 micromol/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.
Tsai
Chia-Wen
CW
Department of Nutrition, Chung Shan Medical University, Taichung 402, Taiwan.
Yang
Jaw-Ji
JJ
Chen
Haw-Wen
HW
Sheen
Lee-Yan
LY
Lii
Chong-Kuei
CK
D000498:Allyl Compounds / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004220:Disulfides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005737:Garlic / Q000737:chemistry*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology*; D015151:Immunoblotting; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology; D013457:Sulfur Compounds / Q000494:pharmacology*
D000498:Allyl Compounds; D004220:Disulfides; D012333:RNA, Messenger; D013440:Sulfides; D013457:Sulfur Compounds; C042577:diallyl trisulfide; C028009:diallyl disulfide; C038491:allyl sulfide; D005982:Glutathione Transferase