Inhibition of Aromatase by Hops, Licorice Species, and their bioactive compounds in Postmenopausal Breast Tissue

Breast cancer risk continues to rise post menopause. Endocrine therapies are employed to prevent postmenopausal breast cancer in high-risk women. However, their adverse effects have reduced acceptability and overall success in cancer preventionatural products such as hops ( Humulus lupulus ) and pharmacopoeial licorice ( Glycyrrhiza ) species, which are used for managing menopausal symptoms, have demonstrated estrogenic and chemopreventive properties. Their beneficial effects on aromatase activity and expression as important factors in postmenopausal breast carcinogenesis are understudied. The presented data show that Gycyrrhiza inflata (GI) has the highest aromatase inhibition potency among these plants. Moreover, phytoestrogens such as 8-prenylnaringenin from hops as well as liquiritigenin and 8-prenylapigenin from licorice are shown to be potent bioactives, in line with computational docking studies. 8-Prenylnaringenin, GI extract, liquiritigenin, and licochalcone A all suppress aromatase expression in postmenopausal women’s breast tissue. Collectively, these data suggest that these natural products may have breast cancer prevention potential for high-risk postmenopausal women. ### Competing Interest Statement The authors have declared no competing interest. * AKR1C3 : Aldoketoreductase 1C3 AI : Aromatase inhibitor CYP : Cytochrome P450 E2 : 17β-Estradiol ER+ : Estrogen receptor positive E1 : Estrone Ex/Em : Excitation/Emission GG : Glycyrrhiza glabra GI : Glycyrrhiza inflata GU : Glycyrrhiza uralensis G6PDH : Glucose-6-phosphate dehydrogenase GST : Glutathione-S-transferase HBSS : Hank’s balanced salt solution HFC : 7-Hydroxy-4-trifluoromethyl coumarin IRB : Institutional Review Board IDT : Integrated DNA Technologies LigC : Isoliquiritigenin IX : Isoxanthohumol LicA : Licochalcone A LigF : Liquiritigenin MFC : 7-methoxy-4-trifluoromethyl coumarin NADPH : Nicotineamide adenine dinucleotide phosphate NQO1 : NADPH:quinone oxidoreductase 1 6-PN : 6-prenylnaringenin 8-PA : 8-prenylapigenin 8-PN : 8-prenylnaringenin PII : Promoter II PI.3 : promoter I.3 PI.4 : Promoter I.4 SERM : Selective estrogen receptor modulators XH : Xanthohumol