Document Detail

Dietary administration of the licorice flavonoid isoliquiritigenin deters the growth of MCF-7 cells overexpressing aromatase.
MedLine Citation:
PMID:  19065667     Owner:  NLM     Status:  MEDLINE    
Licorice is the sweet-tasting rhizomes of a bean plant and is quite commonly used in Western countries for culinary purposes, while it is a medicinal herb in China. Many flavonoids have been isolated from licorice, and their pharmacological properties may be applicable in preventive medicine. Overexposure to estrogen has been implicated in the etiology of breast cancer, and cytochrome P450 (CYP) 19 enzyme, or aromatase, catalyzes the rate-limiting reaction. Phytocompounds that are able to inhibit this enzyme may potentially suppress breast cancer development. In the present study the licorice flavonoid isoliquiritigenin (ILN) was shown to be an aromatase inhibitor in recombinant protein and MCF-7 cells stably transfected with CYP19 (MCF-7aro). ILN displayed a K(i) value of around 3 muM, and it also blocked the MCF-7aro cell growth pertaining to the enzyme activity in vitro. Subsequently, the compound administered in diet was given to ovariectomized athymic mice transplanted with MCF-7aro cells. This mouse model is widely accepted for studying postmenopausal breast cancer. The phytochemical significantly deterred the xenograft growth without affecting the body weight. Subsequently, the flavonoid's effect on CYP19 transcriptional control in vitro was also investigated. At the mRNA level, ILN could also suppress the expression in wild-type MCF-7 cells. Reporter gene assay and real-time PCR verified that the transactivity of CYP19 driven by promoters I.3 and II was suppressed in these cells. Deactivation of C/EBP could be the underlying molecular mechanism. Our study demonstrated that ILN was an inhibitor of aromatase and a potential chemopreventive agent against breast cancer.
Lan Ye; Wai M Gho; Franky L Chan; Shiuan Chen; Lai K Leung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  124     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2008-12-24     Completed Date:  2009-01-23     Revised Date:  2009-09-21    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1028-36     Citation Subset:  IM    
Department of Biochemistry, Chinese University of Hong Kong, NT, Hong Kong.
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MeSH Terms
Aromatase / genetics
Aromatase Inhibitors / administration & dosage*
Breast Neoplasms / enzymology*,  prevention & control*
CCAAT-Enhancer-Binding Proteins / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Chalcones / administration & dosage*
Glycyrrhiza / chemistry*
MAP Kinase Signaling System / drug effects
Mice, Nude
Promoter Regions, Genetic
RNA, Messenger / analysis
Testosterone / pharmacology
Reg. No./Substance:
0/Aromatase Inhibitors; 0/CCAAT-Enhancer-Binding Proteins; 0/Chalcones; 0/RNA, Messenger; 58-22-0/Testosterone; 961-29-5/isoliquiritigenin; EC
Erratum In:
Int J Cancer. 2009 Oct 15;125(8):1995

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