Abstract 2566: The potential role of licorice and its bioactive compounds in promoting a tumor preventive environment in the postmenopausal breast

Abstract

Abstract Introduction: our purpose was to define if licorice and its main bioactive compounds can suppress aromatase expression/activity and Nrf2 dependent detoxification pathways in the postmenopausal breast. This chemopreventive potential has not previously been reported in preclinical models of high-risk postmenopausal breast. Methods: Inhibition of aromatase activity by three licorice extracts (Glycyrrhiza species), and their bioactive compounds, (liquiritigenin; LigF, isoliquiritigenin; LigC, 8-prenylapigenin; 8-PA, and licochalcone A; LicA) 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 effects of treatments on the expression of aromatase (CYP19A1) mRNA and Nrf2 dependent detoxification enzyme NADPH:quinone oxidoreductase 1 (NQO1) in breast microstructures obtained from high risk postmenopausal women were evaluated. Results: Among the three medicinally used licorice species, Glycyrrhiza inflata (GI) showed the highest aromatase inhibitory potency (IC50 ≈ 1 µg/mL). Licorice phytoestrogens, LigF (400 nM or 0.1 µg/mL), and 8-PA (IC50 ≈ 590 nM or 0.2 µg/mL) exhibited the highest potency compared to the other tested licorice compounds. 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 of licorice, LigC and LicA (specific to GI). In breast microstructures obtained from high risk postmenopausal women, expression of aromatase mRNA was suppressed by GI (30%, P < 0.05), LigF (20%, P < 0.05), and LicA (45%, P < 0.05), while the expression of NQO1 mRNA was enhanced by LicA (200%, P < 0.0001). Conclusions: Licorice species, and their bioactive compounds inhibited aromatase activity in vitro. In the breast microstructures, GI, its compounds LigF and LicA suppressed aromatase expression, and LicA enhanced NQO1 induction, significantly. Further studies will further elucidate the potential of these natural products for promoting a breast tumor preventive environment in postmenopausal women. Citation Format: Atieh Hajirahimkhan, Caitlin Howell, Shao-Nong Chen, Susan E. Clare, Guido F. Pauli, Judy L. Bolton, Birgit M. Dietz, Seema A. Khan. The potential role of licorice and its bioactive compounds in promoting a tumor preventive environment in the postmenopausal breast [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2566.