title: The treatment effects of flaxseed-derived secoisolariciresinol diglycoside and its metabolite enterolactone on benign prostatic hyperplasia involve the G protein-coupled estrogen receptor 1.
abstract: Secoisolariciresinol diglucoside (SDG), a lignan extracted from flaxseed, has been shown to suppress benign prostatic hyperplasia (BPH). However, little is known about the mechanistic basis for its anti-BPH activity. The present study showed that enterolactone (ENL), the mammalian metabolite of SDG, shared the similar binding site of G1 on a new type of membranous estrogen receptor, G-protein-coupled estrogen eceptor 1 (GPER), by docking simulations method. ENL and G1 (the specific agonist of GPER) inhibited the proliferation of human prostate stromal cell line WPMY-1 as shown by MTT assay and arrested cell cycle at the G0/G1 phase, which was displayed by propidium iodide staining following flow cytometer examination. Silencing GPER by short interfering RNA attenuated the inhibitory effect of ENL on WPMY-1 cells. The therapeutic potential of SDG in the treatment of BPH was confirmed in a testosterone propionate-induced BPH rat model. SDG significantly reduced the enlargement of the rat prostate and the number of papillary projections of prostatic alveolus and thickness of the pseudostratified epithelial and stromal cells when comparing with the model group. Mechanistic studies showed that SDG and ENL increased the expression of GPER both in vitro and in vivo. Furthermore, ENL-induced cell cycle arrest may be mediated by the activation of GPER/ERK pathway and subsequent upregulation of p53 and p21 and downregulation of cyclin D1. This work, in tandem with previous studies, will enhance our knowledge regarding the mechanism(s) of dietary phytochemicals on BPH prevention and ultimately expand the scope of adopting alternative approaches in BPH treatment.
authors.affiliation: a Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Dushu Lake Higher Education Town, Suzhou 215123, China.|b Department of Urology, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi street, Suzhou 215006, China.
authors.forename: Guan-Yu
authors.initials: GY
authors.lastname: Ren
authors.affiliation: a Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Dushu Lake Higher Education Town, Suzhou 215123, China.|b Department of Urology, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi street, Suzhou 215006, China.
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Chen
authors.affiliation: b Department of Urology, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi street, Suzhou 215006, China.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Chen
authors.affiliation: c Institute of Neuroscience, Soochow University, 199 Renai Road, Dushu Lake Higher Education Town, Suzhou 215123, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Huang
authors.affiliation: a Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Dushu Lake Higher Education Town, Suzhou 215123, China.
authors.forename: Li-Qiang
authors.initials: LQ
authors.lastname: Qin
authors.affiliation: a Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Dushu Lake Higher Education Town, Suzhou 215123, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Chen
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D001665:Binding Sites; D002072:Butylene Glycols / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019587:Dietary Supplements; D019597:Flax / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D005960:Glucosides / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D006027:Glycosides / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009363:Neoplasm Proteins / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012639:Seeds / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002072:Butylene Glycols; C109584:GPER1 protein, human; D005960:Glucosides; D006027:Glycosides; C520305:Gper1 protein, rat; D017705:Lignans; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D015107:4-Butyrolactone; C090142:secoisolariciresinol diglucoside; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone
keywords: G protein-coupled estrogen receptor 1; flaxseed, lignan, benign prostatic hyperplasia; graine de lin; hyperplasie bénigne de la prostate; lignane; récepteur-1 aux œstrogènes couplé aux protéines G