title: Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries.
abstract: Flaxseed has been studied for decades for its health benefits that include anti-cancer, cardio-protective, anti-diabetic, anti-inflammatory properties. The biologically active components that mediate these effects are the omega-3 fatty acids and the lignan, secoisolariciresinol diglucoside. We have previously shown that whole flaxseed supplemented diet decreases the severity and incidence of ovarian cancer while a 15% dose of flaxseed is most protective against inflammation and estrogen-induced chemical and genotoxicity. The objective of this study was to dissect the independent effects of the two flaxseed components on estrogen signaling and metabolism. Two and half year old hens were fed either a control diet, 15% whole flaxseed diet, defatted flax meal diet or 5% flax oil diet for 3 months after which the animals were sacrificed and blood and tissues were harvested. Whole flaxseed diet caused a decrease in expression of ERα. ERα target gene expression was assessed using RT(2) profiler PCR array. Some targets involved in the IGF/insulin signaling pathway (IRS1, IGFBP4, IGFBP5) were downregulated by flaxseed and its components. Flaxseed diet also downregulated AKT expression. A number of targets related to NF-kB signaling were altered by flaxseed diet including a series of targets implicated in cancer. Whole flaxseed diet also affected E2 metabolism by increasing CYP1A1 expression with a corresponding increase in the onco-protective E2 metabolite, 2-methoxyestradiol. The weak anti-estrogens, enterolactone, enterodiol and 2-methoxyestradiol, might be working synergistically to generate a protective effect on the ovaries from hens on whole flaxseed diet by altering the estrogen signaling and metabolism.
authors.affiliation: Department of Physiology, Southern Illinois University School of Medicine, 1125 Lincoln Drive, Life Science II, Room 245B, Carbondale, Illinois 62901, USA.
authors.forename: Anushka
authors.initials: A
authors.lastname: Dikshit
authors.affiliation: Department of Physiology, Southern Illinois University School of Medicine, 1125 Lincoln Drive, Life Science II, Room 245B, Carbondale, Illinois 62901, USA.
authors.forename: Chunqi
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Physiology, Southern Illinois University School of Medicine, 1125 Lincoln Drive, Life Science II, Room 245B, Carbondale, Illinois 62901, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Small
authors.affiliation: Department of Obstetrics and Gynecology, Southern Illinois University School of Medicine, Carbondale, Illinois, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Hales
authors.affiliation: Department of Physiology, Southern Illinois University School of Medicine, 1125 Lincoln Drive, Life Science II, Room 245B, Carbondale, Illinois 62901, USA. Electronic address: dhales@siumed.edu.
authors.forename: Dale Buchanan
authors.initials: DB
authors.lastname: Hales
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D030161:Avian Proteins / Q000378:metabolism; D002645:Chickens; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019587:Dietary Supplements; D004958:Estradiol / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D019597:Flax / Q000737:chemistry; D015870:Gene Expression; D008043:Linseed Oil / Q000008:administration & dosage*; D008099:Liver / Q000201:enzymology; D016328:NF-kappa B / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000517:prevention & control / Q000662:veterinary*; D010053:Ovary / Q000201:enzymology; D011230:Precancerous Conditions / Q000178:diet therapy / Q000378:metabolism / Q000662:veterinary*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D030161:Avian Proteins; D016328:NF-kappa B; D011960:Receptors, Estrogen; D004958:Estradiol; D000077584:2-Methoxyestradiol; D008043:Linseed Oil; D019363:Cytochrome P-450 CYP1A1; D051057:Proto-Oncogene Proteins c-akt
keywords: Estrogen; Flaxseed; Hen; Ovarian cancer