title: Assessment of the proliferative capacity of the flavanones 8-prenylnaringenin, 6-(1.1-dimethylallyl)naringenin and naringenin in MCF-7 cells and the rat mammary gland.
abstract: 8-Prenylnaringenin (8-PN) and naringenin (Nar) are phytoestrogens found in food items and nutritional supplements, while 6-(1.1-dimethylallyl)naringenin (6-DMAN) is a component of an African plant. Besides their assumed beneficial effects they may promote mammary and endometrial cancer. We therefore assessed their proliferative and estrogenic potential on the mammary gland in vitro and in vivo. In competitive estrogen receptor (ER) ligand binding assays 8-PN displayed a high relative binding affinity for both ERs with a preference for ERα and had the strongest mitotic effect on MCF-7 cells among the test substances. In a three day exposure in young adult ovariectomized female rats 15 mg/kg 8-PN had the highest capacity to increase the number of terminal end buds (TEB) in the mammary gland and stimulated expression of proliferation markers in epithelial ductal cells, followed by 6-DMAN and Nar, but overall their capacity to stimulate proliferation was weak in comparison to 17β-Estradiol (E2).
authors.affiliation: Institute of Zoology, Technische Universität Dresden, Zellescher Weg 20b, 01062 Dresden, Germany. Electronic address: Janina.Helle@tu-dresden.de.
authors.forename: Janina
authors.initials: J
authors.lastname: Helle
authors.affiliation: Institute of Zoology, Technische Universität Dresden, Zellescher Weg 20b, 01062 Dresden, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Kräker
authors.affiliation: Institute of Zoology, Technische Universität Dresden, Zellescher Weg 20b, 01062 Dresden, Germany.
authors.forename: Manuela I
authors.initials: MI
authors.lastname: Bader
authors.affiliation: Institute of Zoology, Technische Universität Dresden, Zellescher Weg 20b, 01062 Dresden, Germany.
authors.forename: Annekathrin M
authors.initials: AM
authors.lastname: Keiler
authors.affiliation: Institute of Zoology, Technische Universität Dresden, Zellescher Weg 20b, 01062 Dresden, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Zierau
authors.affiliation: Institute of Zoology, Technische Universität Dresden, Zellescher Weg 20b, 01062 Dresden, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Vollmer
authors.affiliation: Gen(*)NY(*)Sis Center for Excellence in Cancer Genomics (Cancer Research Center), University at Albany, One Discovery Drive, Rensselaer, NY 12144-2345, United States.
authors.forename: JoEllen
authors.initials: J
authors.lastname: Welsh
authors.affiliation: Institute of Zoology, Technische Universität Dresden, Zellescher Weg 20b, 01062 Dresden, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Kretzschmar
mesh_terms: D066258:Amphiregulin / Q000378:metabolism; D000818:Animals; D002364:Caseins / Q000378:metabolism; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D044950:Flavanones / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D019394:Ki-67 Antigen / Q000378:metabolism; D061986:MCF-7 Cells; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011917:Rats, Inbred Lew; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: C462031:6-(1,1-dimethylallyl)naringenin; C119737:8-prenylnaringenin; D066258:Amphiregulin; D002364:Caseins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D044950:Flavanones; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D011980:Receptors, Progesterone; C005273:naringenin
keywords: 6-(1.1-Dimethylallyl)naringenin; 8-Prenylnaringenin; Hormone replacement therapy; MCF-7 cells; Naringenin; Uterotrophic assay