Flaxseed-Derived Enterolactone Is Inversely Associated with Tumor Cell Proliferation in Men with Localized Prostate Cancer

Azrad, Maria; Vollmer, Robin T.; Madden, John F.; Dewhirst, Mark W.; Polascik, Thomas J.; Snyder, Denise C.; Ruffin, Mack T.; Moul, Judd W.; Brenner, Dean E.; Demark‐Wahnefried, Wendy

doi:10.1089/jmf.2012.0159

Cited by 59 publications

(26 citation statements)

References 25 publications

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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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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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“…A significant concentration of enterolactone has been reported in bovine milk (Antignac et al, 2004). In general, under normal dietary conditions, enterolactone is the enterolignan that reaches the highest concentration in plasma (Kuijsten et al, 2006;Högger, 2013) and is the most effective metabolite in the inhibition of cell proliferation (Corsini et al, 2010;Azrad et al, 2013). Owing to the potential beneficial effects of enterolactone and the complex relationship between the colonic environment and other factors contributing to systemic exposure of such compounds to ABC transporters, a study of the interaction of ABCG2 with enterolactone could be of particular relevance.…”

Section: Introductionmentioning

confidence: 99%

Role of ABCG2 in Transport of the Mammalian Lignan Enterolactone and its Secretion into Milk in Abcg2 Knockout Mice

et al. 2014

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Lignans are phytoestrogens that are metabolized by the gut microbiota to enterodiol and enterolactone, the main biologically active enterolignans. Substantial interindividual variation in plasma concentration and urinary excretion of enterolignans has been reported, this being determined, at least in part, by the intake of lignan precursors, the gut microbiota, and the host's phase 2 conjugating enzyme activity. However, the role of ATP-binding cassette (ABC) transporters in the transport and disposition of enterolactone has not been reported so far. Active transport assays using parental and Madin-Darby canine kidney epithelial cells transduced with murine and human ABCG2 showed a significant increase in apically directed translocation of enterolactone in transduced cells, which was confirmed by using the selective ABCG2 inhibitor Ko143. In addition, enterolactone also inhibited transport of the antineoplastic agent mitoxantrone as a model substrate, with inhibition percentages of almost 40% at 200 mM for human ABCG2. Furthermore, the endogenous levels in plasma and milk of enterolactone in wild-type and Abcg2(2/2) knockout female mice were analyzed. The milk/ plasma ratio decreased significantly in the Abcg2 (2/2) phenotype, as compared with the wild-type mouse group (0.4 6 0.1 as against 6.4 6 2.6). This paper is the first to report that enterolactone is a transported substrate and therefore most probably a competitive inhibitor of ABCG2, which suggests it has a role in the interindividual variations in the disposition of enterolactone and its secretion into milk. The inhibitory activity identified provides a solid basis for further investigation in possible food-drug interactions. IntroductionThe ATP-binding cassette (ABC) subfamily G2 (ABCG2) protein is apically expressed ABC membrane transporter that mediates the active and outward transport of a wide range of anticancer drugs, dietary compounds, food carcinogens, and antibiotics from cells (van Herwaarden et al., 2003;Merino et al., 2005;Vlaming et al., 2009). In recent years, its role as a transporter of phytoestrogens and their conjugated metabolites has gained special relevance (Zhu et al., 2010;Alvarez et al., 2011;Tan et al., 2013).ABCG2 is found in tumor cells, but also in the cells of a variety of normal tissues involved in the uptake and elimination of compounds, such as enterocytes, hepatocytes, and cells of the proximal tubules of the kidney. The apical localization in these cells allows ABCG2 to mediate hepatobiliary and urinary elimination and to function as a barrier to uptake from the gut lumen (van Herwaarden and Schinkel, 2006). In addition, induced expression of ABCG2 in the lactating mammary gland supports its important role in the active secretion of several xenobiotics and beneficial compounds such as vitamins into milk Merino et al., 2006;van Herwaarden et al., 2007).Dietary intake of lignans and their derivatives, as part of a healthy diet, has been associated with protective effects against a number of chronic diseases (Hu e...

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“…Tinakaczor (2014) (7). extracted data from above study and find that flaxseeds can reduce aggressiveness of an already existing tumor of prostate.…”

Section: Discussionmentioning

confidence: 99%

Flax Seeds In Prostate Cancer A Case report- self experienced.

Singh¹

2017

IOSR JDMS

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Flaxseed-Derived Enterolactone Is Inversely Associated with Tumor Cell Proliferation in Men with Localized Prostate Cancer

Cited by 59 publications

References 25 publications

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

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

Role of ABCG2 in Transport of the Mammalian Lignan Enterolactone and its Secretion into Milk in Abcg2 Knockout Mice

Flax Seeds In Prostate Cancer A Case report- self experienced.

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