Hops extracts and key bioactive compounds activate both aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) pathways

ZANARDI MV; KRETZSCHMAR G; ZIERAU O; WOBER J; DURANDO M; GASTIAZORO MP; VARAYOUD J

Essen

Encuentro; Young Active Research in Endocrinology (YARE) Meeting; 2019

Technische Univeritat Dresden

The increased cancer risk associated with hormone therapies has produced an increase in the usage of plant derived extracts like from Humulus lupulus L. (hops) as a natural alternative to alleviate menopausal symptoms. The rationale behind it is that hops contains substances that potentially modulate the chemical estrogen carcinogenesis pathway and could protect women from cancer. Our aim was to determine the effects of hops extracts (HE) and its compounds, 6-prenylnaringenin (6-PN) and 8-prenylnaringenin (8-PN), on endometrial cells proposing mechanistic pathways of the interaction between AhR and ER. Different doses of HE (7; 0.7 and 0.07 µg/ml), 6-PN (10-5 to 10-7 M) and 8-PN (10-6 to 10-8M) were studied in an endometrial carcinoma human cell line (Ishikawa cells) transfected with an estrogen responsive element (ERE) and dioxin response element (DRE) luciferase reporter plasmid. We also analysed the induced estrogen responsive effect on alkaline phosphatase activity. 8-PN, significantly and dose-dependently, 6-PN (10-5 and 10-6M) and hops (7 µg/ml) in higher dosage increased ERE-luciferase activity. The hops extract (7 and 0.7 µg/ml) and the highest dose of 6-PN increased DRE activation. Finally, HE (0.7 µg/ml), 6-PN (10-6M) and 8-PN (10-6to 10-8M) induced the estrogen responsive effect on alkaline phosphatase activity. These results showed that the estrogenicity of hops is a function not only of 8-PN, but also 6-PN, and suggested that HE, through its compounds, acted as an agonist of both AhR and ER.