Dietary administration of the licorice flavonoid isoliquiritigenin deters the growth of MCF-7 cells overexpressing aromatase.
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.
Ye
Lan
L
Department of Biochemistry, Chinese University of Hong Kong, NT, Hong Kong.
Gho
Wai M
WM
Chan
Franky L
FL
Chen
Shiuan
S
Leung
Lai K
LK
D000818:Animals; D001141:Aromatase / Q000235:genetics; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000517:prevention & control*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000008:administration & dosage*; D005260:Female; D006035:Glycyrrhiza / Q000737:chemistry*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D010052:Ovariectomy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D013739:Testosterone / Q000494:pharmacology
D047072:Aromatase Inhibitors; D022762:CCAAT-Enhancer-Binding Proteins; D047188:Chalcones; D012333:RNA, Messenger; D013739:Testosterone; C040920:isoliquiritigenin; D001141:Aromatase