title: Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus.
abstract: Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for hERα and hERβ with IC50 values of 1.20 ×10(-7) g/ml and 1.00×10(-7) g/ml, respectively. LNE induced 17β-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on hER α and β than other fractions. Our results indicate that LNE had higher binding affinities for hERβ than hERα, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.
authors.affiliation: College of Pharmacy, College of Science, Sookmyung Women's University, Seoul 140-742.
authors.forename: Hye-Na
authors.initials: HN
authors.lastname: Ahn
authors.affiliation: College of Pharmacy, College of Science, Sookmyung Women's University, Seoul 140-742.
authors.forename: Si-Yeon
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, College of Science, Sookmyung Women's University, Seoul 140-742.
authors.forename: Gyu-Un
authors.initials: GU
authors.lastname: Bae
authors.affiliation: Department of Medical and Pharmaceutical Science, College of Science, Sookmyung Women's University, Seoul 140-742.
authors.forename: Minsun
authors.initials: M
authors.lastname: Chang
authors.affiliation: Department of Medical and Pharmaceutical Science, College of Science, Sookmyung Women's University, Seoul 140-742.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Medical and Pharmaceutical Science, College of Science, Sookmyung Women's University, Seoul 140-742.
authors.forename: Xiyuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, Cheongwon 363-883, Republic of Korea.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Pei
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, Cheongwon 363-883, Republic of Korea.
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Chin
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang 410-820.
authors.forename: Joongku
authors.initials: J
authors.lastname: Lee
authors.affiliation: International Biological Material Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon 305-806.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: College of Pharmacy, College of Science, Sookmyung Women's University, Seoul 140-742.
authors.forename: Yun Seon
authors.initials: YS
authors.lastname: Song
keywords: Estrogen receptor; Larrea nitida; Lignan; MCF-7 cell; Phytoestrogen; Uterus