title: Enterolactone restricts the proliferation of the LNCaP human prostate cancer cell line in vitro.
abstract: Ecological data suggest a long-term diet high in plant material rich in biologically active compounds, such as the lignans, can significantly influence the development of prostate cancer over the lifetime of an individual. The capacity of a pure mammalian lignan, enterolactone (ENL), to influence the proliferation of the LNCaP human prostate cancer cell line was investigated as a function of cell density, metabolic activity, expression and secretion of prostate specific antigen (PSA), cell cycle profile, and the expression of genes involved in development and progression of prostate cancer. Treatment with a subcytotoxic concentration of ENL (60 muM for 72 h) was found to reduce: cell density (57.5%, SD 7.23, p < 0.001), metabolic activity (55%, SD 0.03, p < 0.001), secretion of PSA (48.50% SD 4.74, p = 0.05) and induce apoptosis (8.33-fold SD 0.04, p = 0.001) compared to untreated cells. Cotreatment with 10 muM etoposide was found to increase apoptosis by 50.17% (SD 0.02, p < 0.001). Additionally, several key genes (e. g. MCMs, survivin and CDKs) were beneficially regulated by ENL treatment (p < 0.05). The data suggest that the antiproliferative activity of ENL is a consequence of altered expression of cell cycle associated genes and provides novel molecular evidence for the antiproliferative properties of a pure lignan in prostate cancer.
authors.affiliation: Northern Ireland Centre for Food and Health, Biomedical Sciences Research Institute, University of Ulster, Coleraine, Northern Ireland. mark.mccann@agresearch.co.nz
authors.forename: Mark J
authors.initials: MJ
authors.lastname: McCann
authors.forename: Chris I R
authors.initials: CI
authors.lastname: Gill
authors.forename: Trevor
authors.initials: T
authors.lastname: Linton
authors.forename: D
authors.initials: D
authors.lastname: Berrar
authors.forename: Hugh
authors.initials: H
authors.lastname: McGlynn
authors.forename: Ian R
authors.initials: IR
authors.lastname: Rowland
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D048789:Phytoestrogens / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen / Q000187:drug effects / Q000235:genetics; D011471:Prostatic Neoplasms / Q000473:pathology
chemical_list: D017705:Lignans; D048789:Phytoestrogens; D017430:Prostate-Specific Antigen; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone