Dietary administration of the licorice flavonoid isoliquiritigenin deters the growth of MCF-7 cells overexpressing aromatase

Abstract

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. Pin tocom pounds 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 ceils stably transfected with CYP 19 (MCF-7aro). ILN displayed a k 1, value of around 3 μM, 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 phytochemicai signilcantly deterred the xenograft growth without affecting the body weight. Subsequently, the flavo-noid's effect on CYP19 transcriptional control in vitro was also investigated. At the tiiRNA level, ILN could also suppress the expression in wild-tvpe MCF-7 cells. Reporter gene assay and real-time PVR verified that the transactivity of CYP19 driven by promoters 1.3 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. © 2008 Wilev-Liss, Inc.