Uncovering molecular events associated with the chemosuppressive effects of flaxseed: a microarray analysis of the laying hen model of ovarian cancer

Hales, Karen; Speckman, Sheree C.; Kurrey, Nawneet K.; Hales, Dale B.

doi:10.1186/1471-2164-15-709

Cited by 16 publications

(20 citation statements)

References 53 publications

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“…Marek's disease virus, reticuloendotheliosis, avian leukemia and tumors of unknown etiology. Some authors indicate that cell cultures from malignant birds may significantly expand prospects in viral oncology and chemoprevention trials (HALES et al 2014;MOTIANI et al 2013). The pursuit of stem cell markers in the fallopian tube has been reflected in recent publications.…”

Section: Discussionmentioning

confidence: 99%

Efficient Source of Cells in Proximal Oviduct for Testing Non-Viral Expression Constructs in the Chicken Bioreactor Model and for Other <I>in Vitro</I> Studies

Stadnicka

Bodnar

Marszałek

et al. 2016

folia biol (krakow)

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Efficient source of cells in proximal oviduct for testing non-viral expression constructs in the chicken bioreactor model and for other in vitro studies. Folia Biologica (Kraków) 64: 37-46. This work shows the usefulness of chicken oviduct epithelial cells (COEC) in evaluating the efficacy of non-viral expression vectors carrying human therapeutic genes. Secondly, an efficient source of progenitor COEC for in vitro studies is described. Within the distal part of the oviduct, weak to moderate expression of a trans membrane glycoprotein (CD44) was observed. Single cells presenting only weak expression of CD44 were found in magnum sections. in vitro cultured oviduct cells originating from the distal oviduct were suitable for subculturing and showed a stable proliferation potential up to the 2nd passage. However, the pavimentous epithelial-like morphology of COEC was progressively lost over time and mainly a fibroblast-like monolayer was established in consecutive passages. Moreover, various commercial transfection agents including FuGENE6 and XtremeGENE9 DNA were used to optimize delivery of human interferon alfa-2a, (IFNá2a) a therapeutic protein gene under an ovalbumin promoter. The transfection efficiency of adherent COEC was estimated for up to 40% at a ratio of 6:1 of transfectant to pOVA5EIFN + GFP plasmid. Expression of IFNá2a was confirmed by western blotting in transformed COEC. In conclusion, the population of epithelial progenitor cells sourced from the distal oviduct can significantly contribute to in vitro culture of COEC, representing an efficient model to develop the production of avian bioreactors and other in vitro studies related to oviduct tissue.

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Section: Discussionmentioning

confidence: 99%

Efficient Source of Cells in Proximal Oviduct for Testing Non-Viral Expression Constructs in the Chicken Bioreactor Model and for Other <I>in Vitro</I> Studies

Stadnicka

Bodnar

Marszałek

et al. 2016

folia biol (krakow)

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“…Nutritional antioxidant cocktails have also been shown to be radioprotective of hematopoietic cells and even boost animal survival [49] in mice exposed to spacerelevant radiation such as protons and gamma radiation. Wholegrain flaxseed (FS) and its bioactive metabolic components have been extensively studied in other organ systems and have proven to be beneficial, mostly in regards to cancer including breast [50], colon [51,52], ovarian [53,54] or prostate [55] cancer. Our group was the first to show that dietary FS supplementation could also reduce lung inflammation and lipid peroxidation in murine models of acid aspiration and hyperoxia [12] and more recently, in lung ischemia/reperfusion injury related to transplantation damage [13].…”

Section: Discussionmentioning

confidence: 99%

Flaxseed Mitigates Acute Oxidative Lung Damage in a Mouse Model of Repeated Radiation and Hyperoxia Exposure Associated with Space Exploration

Pietrofesa

Solomides

Christofidou‐Solomidou

2014

J Pulm Respir Med

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Background Spaceflight missions may require crewmembers to conduct extravehicular activities (EVA). Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours and be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health. We have developed a mouse model of total body radiation and hyperoxia exposure and identified acute damage of lung tissues. In the current study we evaluated the usefulness of dietary flaxseed (FS) as a countermeasure agent for such double-hit exposures. Methods We evaluated lung tissue changes 2 weeks post-initiation of exposure challenges. Mouse cohorts (n=5/group) were pre-fed diets containing either 0% FS or 10% FS for 3 weeks and exposed to: a) normoxia (Untreated); b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) 3 times per week for 2 consecutive weeks, where 8-hour hyperoxia treatments were spanned by normoxic intervals. Results At 2 weeks post challenge, while control-diet fed mice developed significant lung injury and inflammation across all challenges, FS protected lung tissues by decreasing bronchoalveolar lavage fluid (BALF) neutrophils (p<0.003) and protein levels, oxidative tissue damage, as determined by levels of malondialdehyde (MDA) (p<0.008) and nitrosative stress as determined by nitrite levels. Lung hydroxyproline levels, a measure of lung fibrosis, were significantly elevated in mice fed 0% FS (p<0.01) and exposed to hyperoxia/radiation or the combination treatment, but not in FS-fed mice. FS also decreased levels of a pro-inflammatory, pro-fibrogenic cytokine (TGF-β1) gene expression levels in lung. Conclusion Flaxseed mitigated adverse effects in lung of repeat exposures to radiation/hyperoxia. This data will provide useful information in the design of countermeasures to early tissue oxidative damage associated with space exploration.

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“…EPA and DHA can get incorporated into the cell membrane and shift the equilibrium of PG (prostaglandin) synthesis to a less inflammatory type (PGE3) [28] as previously demonstrated by our group [29]. In addition, E-cadherin, a marker characteristically upregulated in human epithelial ovarian cancers as well as in the hen ovarian tumor [30], is significantly downregulated in ovarian tumors from hens fed a flaxseed supplemented diet [31]. Flaxseed lignan metabolites, EL and ED, have been shown to decrease estrogen dependent receptor activation in breast cancer cells and flaxseed diet also results in decreased ERα expression in the chicken ovary[17].…”

Section: Introductionmentioning

confidence: 94%

“…[17, 26, 30, 31, 33], but it is important to determine the precise pathways targeted by the biologically active components of flaxseed that affect the expression of a wide range of cancer targets.…”

Section: Introductionmentioning

confidence: 99%

Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries

Dikshit

Gao

Small

et al. 2016

The Journal of Steroid Biochemistry and Molecular Biology

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Flaxseed has been studied for decades for its health benefits that include anti-cancer, cardioprotective, anti-diabetic, anti-inflammatory properties. The biologically active components that mediate these effects are the omega-3 fatty acids and the lignan, secoisolaricirescinol 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 RT2 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-κB 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.

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Uncovering molecular events associated with the chemosuppressive effects of flaxseed: a microarray analysis of the laying hen model of ovarian cancer

Cited by 16 publications

References 53 publications

Efficient Source of Cells in Proximal Oviduct for Testing Non-Viral Expression Constructs in the Chicken Bioreactor Model and for Other <I>in Vitro</I> Studies

Efficient Source of Cells in Proximal Oviduct for Testing Non-Viral Expression Constructs in the Chicken Bioreactor Model and for Other <I>in Vitro</I> Studies

Flaxseed Mitigates Acute Oxidative Lung Damage in a Mouse Model of Repeated Radiation and Hyperoxia Exposure Associated with Space Exploration

Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries

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