title: Modulation of breast cancer cell survival by aromatase inhibiting hop (Humulus lupulus L.) flavonoids.
abstract: Hop flavonoids are being regarded as attractive molecules to prevent or treat certain forms of cancer. Studies have focused mainly on xanthohumol, the most abundant prenylated chalcone existing in hops extract. However, during the production of beer, or after its ingestion, xanthohumol originates different metabolites, among which isoxanthohumol and 8-prenylnaringenin. The aim of this work was to study the effect of the prenylflavonoids xanthohumol, isoxanthohumol and 8-prenylnaringenin on the breast cancer Sk-Br-3 cell line proliferation, apoptosis and activity of the enzyme aromatase (estrogen synthase). Aromatase activity was determined by a tritiated water assay, cell proliferation was assessed by [(3)H]thymidine incorporation, sulforhodamine B protein measurement and Ki-67 immunostaining and apoptosis was determined by TUNEL. Our results show that all tested prenylflavonoids were able to inhibit aromatase activity and thus, estrogen formation. Additionally, breast cancer cell line proliferation was decreased and apoptosis induced by all three compounds. The presence of 17beta-estradiol in treatment medium was able to revert the effect of the prenylflavonoids on cellular proliferation. These observations strengthen the idea that hop flavonoids may have anti-breast cancer effects and shed new light on a possible mechanism of action by which these effects occur, namely through their ability to decrease estrogen synthesis.
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. rosariom@med.up.pt
authors.forename: Rosário
authors.initials: R
authors.lastname: Monteiro
authors.forename: Ana
authors.initials: A
authors.lastname: Faria
authors.forename: Isabel
authors.initials: I
authors.lastname: Azevedo
authors.forename: Conceição
authors.initials: C
authors.lastname: Calhau
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004261:DNA Replication; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D027582:Humulus / Q000737:chemistry*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling
chemical_list: D047072:Aromatase Inhibitors; D005419:Flavonoids