Hops (humulus Lupulus) Inhibits Estrogen Metabolism in Non-tumorigenic Human Breast Epithelial Cells (MCF-10A Cells)

Long-term exposure to estrogen increases the risk of hormone dependent cancers in women. Estrogen induced cell proliferation in estrogen receptor positive cells (hormonal pathway), and the formation of reactive estrogen o-quinones mediated by cytochrome P450s (chemical pathway) are believed to contribute to the estrogen carcinogenesis mechanism [1]. Estrogens are oxidized by P450 1A1/1A2 to the catechol metabolites, 2-hydroxyestradiol, and by P450 1B1 to 4- hydroxyestradiol. Both catechols are further oxidized to form electrophilic o-quinones that can react with DNA and proteins. For years, plant extracts have been used worldwide, as dietary supplements for women's health particularly for menopausal symptom relief. Mounting evidence suggests that botanical dietary supplements have chemopreventive properties that could specifically protect women from the carcinogenic effects of endogenous estrogens through modulation of both hormonal and chemical mechanisms. The current study focuses on elucidating the influence of these extensively utilized botanicals on estrogen metabolism in normal breast epithelial cells (MCF-10A). MCF-10A cells are estrogen receptor negative non-tumorigenic human breast epithelial cells, which can be transformed into a malignant phenotype with estradiol [2]. After treatment of MCF-10A cells with estradiol and botanical extracts, estrogen metabolites were analyzed using a sensitive LC-MS/MS method. Among the botanical extracts tested, hops (Humulus lupulus) showed a significant reduction in catechol estrogen formation whereas black cohosh (Cimicifuga racemosa) had little effect. These data suggest that the hop extract might possess chemopreventive activity through inhibition of genotoxic estrogen quinone formation in addition to its known antioxidant and induction of detoxification enzyme capabilities. Acknowledgment: Support for this work was provided by NIH CA130037 and P50 AT00155.