Document Detail

Modulation of CYP1B1 and CYP1A1 gene expression and activation of aryl hydrocarbon receptor by Ginkgo biloba extract in MCF-10A human mammary epithelial cells.
MedLine Citation:
PMID:  19794518     Owner:  NLM     Status:  MEDLINE    
The aryl hydrocarbon receptor (AhR) signaling pathway regulates the production of CYP1B1 and CYP1A1, which catalyze the bioactivation of various procarcinogens. In the present study, we investigated the effect of Ginkgo biloba extract and some of its chemical constituents on CYP1B1 and CYP1A1 gene expression and AhR activity in cultured MCF-10A human mammary epithelial cells. Treatment of MCF-10A cells with noncytotoxic concentrations of G. biloba extract (25-300 microg/mL for 24 or 48 h) increased CYP1B1 and CYP1A1 mRNA expression, which was accompanied by an increase in CYP1-mediated ethoxyresorufin O-dealkylation activity. The inductive effects of G. biloba extract were attenuated by an AhR antagonist (3',4'-dimethoxyflavone). G. biloba extract (25-300 microg/mL) increased AhR-dependent reporter activity, as determined in MCF-10A cells transfected with an AhR-regulated luciferase reporter plasmid (pGudluc6.1). Bilobalide and ginkgolides A, B, C, and J were not responsible for the modulation of CYP1B1 and CYP1A1 gene expression or AhR activation by G. biloba extract. In contrast, quercetin increased CYP1B1 and CYP1A1 gene expression and activated AhR, whereas kaempferol and isorhamnetin suppressed constitutive CYP1B1 expression and antagonized AhR activation by benzo[a]pyrene. Overall, our findings provide an impetus for future investigations on the effect of G. biloba extract in CYP1-mediated chemical carcinogenesis.
Ganesh Rajaraman; Guixiang Yang; Jie Chen; Thomas K H Chang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  87     ISSN:  1205-7541     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-10-01     Completed Date:  2010-03-30     Revised Date:  2014-01-08    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  674-83     Citation Subset:  IM    
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MeSH Terms
Aryl Hydrocarbon Hydroxylases
Cell Culture Techniques
Cell Line
Cell Survival / drug effects
Cytochrome P-450 CYP1A1 / genetics*
Cytochrome P-450 Enzyme System / genetics*
DNA, Complementary / genetics
Epithelial Cells / drug effects*,  enzymology
Gene Expression / drug effects*
Genes, Reporter
Ginkgo biloba / chemistry*
Luciferases, Firefly / genetics
Luciferases, Renilla / genetics
Plant Extracts / isolation & purification,  pharmacology*
RNA / genetics
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/DNA, Complementary; 0/Plant Extracts; 63231-63-0/RNA; 9035-51-2/Cytochrome P-450 Enzyme System; EC, Renilla; EC, Firefly; EC Hydrocarbon Hydroxylases; EC P-450 CYP1A1; EC P-450 CYP1B1

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