Abstract PS8-10: Inhibition of estrogen biosynthesis by hops, licorice species, and their bioactive compounds
Authors: Hajirahimkhan Atieh , Howell Caitlin , Dunlap Tareisha , Chen Shao-Nong , Clare Susan E. , Pauli Guido F. , Bolton Judy L. , Dietz Birgit M. , Khan Seema A. 
Published: February 2021

Introduction: Breast cancer risk continues to rise following menopause, despite the cessation of ovarian estrogen synthesis. Pathways involving increased aromatase activity and inflammation in the breast microenvironment are implicated. Their concerted disruption could be protective against breast cancer. Popular botanicals for menopausal health, such as hops (Humulus lupulus), three licorice species (Glycyrrhiza glabra, Glycyrrhiza inflata, Glycyrrhiza uralensis) extracts, and their bioactive compounds have shown estrogenic and chemopreventive properties in vitro and in vivo. Their effects on aromatase expression and activity, and on inflammatory responses in the breast are not well characterized.Methods: Inhibition of aromatase activity by hops extract, its compounds (8-prenylnaringenin, 6-prenylnaringenin, and xanthohumol); three licorice extracts, and their bioactive compounds, (liquiritigenin, isoliquiritigenin, 8-prenylapigenin, and licochalcone A) were evaluated fluorometrically, using aromatase supersomes. Computational docking was performed to assess the binding of the bioactive compounds to the binding pocket of aromatase crystal structure compared to the known aromatase inhibitors, letrozole (non-steroidal) and exemestane (steroidal). Using qPCR, the effect of treatments on aromatase mRNA expression in breast microstructures of menopausal women was evaluated. The effects of hops and licorice on transactivation of NF-kB in MCF-7 breast cancer cells were studied, using a luciferase assay.Results: Among the extracts, one of the licorice species, Glycyrrhiza inflata showed the highest aromatase inhibitory potency (IC50 ≈ 1 µg/mL). Among the compounds, the phytoestrogens 8-prenylnaringenin (IC50 = 50 nM or 17 ng/mL) from hops, liquiritigenin (400 nM or 0.1 µg/mL), and 8-prenylapigenin (IC50 ≈ 590 nM or 0.2 µg/mL) from licorice exhibited the highest potency. Computational docking suggested that these phytoestrogens bind to the aromatase binding pocket like the aromatase inhibitor, letrozole. This effect was not observed with non-estrogenic bioactive compounds including 6-prenylnaringenin and xanthohumol from hops as well as isoliquiritigenin and licochalcone A from licorice. Hops and 8-prenylnaringenin reduced aromatase expression in breast microstructures by 60% (P &lt; 0.05). Moreover, hops and licorice extracts suppressed NF-kB-luciferase activity by 70% in MCF-7 cells (P&lt; 0.01). Conclusions: Hops, licorice species, and their phytoestrogens inhibit aromatase activity and expression. The extracts suppress NF-kB transactivation in MCF-7 cells, suggesting inhibition of inflammatory response. Further studies will better elucidate the potential of these popular botanicals and their bioactive compounds for preventing breast cancer in menopausal women.

Citation Format: Atieh Hajirahimkhan, Caitlin Howell, Tareisha Dunlap, Shao-Nong Chen, Susan E. Clare, Guido F. Pauli, Judy L. Bolton, Birgit M. Dietz, Seema A. Khan. Inhibition of estrogen biosynthesis by hops, licorice species, and their bioactive compounds [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-10.