Document Detail

Sulforaphane and alpha-lipoic acid upregulate the expression of the pi class of glutathione S-transferase through c-jun and Nrf2 activation.
MedLine Citation:
PMID:  20237067     Owner:  NLM     Status:  MEDLINE    
The anticarcinogenic effect of dietary organosulfur compounds has been partly attributed to their modulation of the activity and expression of phase II detoxification enzymes. Our previous studies indicated that garlic allyl sulfides upregulate the expression of the pi class of glutathione S-transferase (GSTP) through the activator protein-1 pathway. Here, we examined the modulatory effect of sulforaphane (SFN) and alpha-lipoic acid (LA) or dihydrolipoic acid (DHLA) on GSTP expression in rat Clone 9 liver cells. Cells were treated with LA or DHLA (50-600 micromol/L) or SFN (0.2-5 micromol/L) for 24 h. Immunoblots and real-time PCR showed that SFN, LA, and DHLA dose dependently induced GSTP protein and mRNA expression. Compared with the induction by the garlic organosulfur compound diallyl trisulfide (DATS), the effectiveness was in the order of SFN > DATS > LA = DHLA. The increase in GSTP enzyme activity in cells treated with 5 micromol/L SFN, 50 micromol/L DATS, and 600 micromol/L LA and DHLA was 172, 75, 122, and 117%, respectively (P < 0.05). A reporter assay showed that the GSTP enhancer I (GPEI) was required for GSTP induction by the organosulfur compounds. Electromobility gel shift assays showed that the DNA binding of GPEI to nuclear proteins reached a maximum at 0.5-1 h after SFN, LA, and DHLA treatment. Super-shift assay revealed that the transcription factors c-jun and nuclear factor erythroid-2 related factor 2 (Nrf2) were bound to GPEI. These results suggest that SFN and LA in either its oxidized or reduced form upregulate the transcription of the GSTP gene by activating c-jun and Nrf2 binding to the enhancer element GPEI.
Chong-Kuei Lii; Kai-Li Liu; Yi-Ping Cheng; Ai-Hsuan Lin; Haw-Wen Chen; Chia-Wen Tsai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-17
Journal Detail:
Title:  The Journal of nutrition     Volume:  140     ISSN:  1541-6100     ISO Abbreviation:  J. Nutr.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-21     Completed Date:  2010-05-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  885-92     Citation Subset:  IM    
Department of Nutrition, China Medical University, Taichung 404, Taiwan.
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MeSH Terms
Allyl Compounds / pharmacology*
Antineoplastic Agents, Phytogenic / pharmacology
Cell Line
DNA / metabolism
DNA-Binding Proteins / metabolism
Enzyme Activators / pharmacology*
Garlic / chemistry
Gene Expression Regulation, Enzymologic / drug effects*
Glutathione Transferase / genetics,  metabolism*
Liver / drug effects,  enzymology
NF-E2-Related Factor 2 / genetics,  metabolism
Nuclear Proteins / metabolism
Plant Extracts / pharmacology*
Proto-Oncogene Proteins c-jun / genetics,  metabolism
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sulfides / pharmacology*
Thioctic Acid / analogs & derivatives,  pharmacology*
Thiocyanates / pharmacology*
Up-Regulation / drug effects
Reg. No./Substance:
0/Allyl Compounds; 0/Antineoplastic Agents, Phytogenic; 0/DNA-Binding Proteins; 0/Enzyme Activators; 0/NF-E2-Related Factor 2; 0/Nuclear Proteins; 0/Plant Extracts; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 0/Sulfides; 0/Thiocyanates; 2050-87-5/diallyl trisulfide; 4478-93-7/sulforafan; 62-46-4/Thioctic Acid; 9007-49-2/DNA; EC Transferase

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