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Depression: 21st Century Solutions + The Dark Side of Wheat

Abstract Title:

Chemopreventive effects of dietary eicosapentaenoic acid supplementation in an experimental myeloid leukemia.

Abstract Source:

Cancer Prev Res (Phila). 2015 Aug 19. Epub 2015 Aug 19. PMID: 26290393

Abstract Author(s):

Emily R Finch, Avinash K Kudva, Michael D Quickel, Laura L Goodfield, Mary J Kennett, Jay Whelan, Robert F Paulson, K Sandeep Prabhu

Article Affiliation:

Emily R Finch

Abstract:

Current therapies for treatment of myeloid leukemia do not eliminate leukemia stem cells (LSC), leading to disease relapse. In this study, we supplemented mice with eicosapentaenoic acid (EPA, C20:5), a polyunsaturated omega-3 fatty acid, at pharmacological levels, to examine if the endogenous metabolite, cyclopentenone prostaglandin delta-12 PGJ3 (Δ12-PGJ3), was effective in targeting LSCs in experimental leukemia. EPA supplementation for eight weeks resulted in enhanced endogenous production of Δ12-PGJ3 that was blocked by indomethacin, a cyclooxygenase inhibitor. Using a murine model of chronic myelogenous leukemia (CML) induced by bone marrow transplantation of BCR-ABL-expressing hematopoietic stem cells, mice supplemented with EPA showed a decrease in the LSC population, reduced splenomegaly and leukocytosis, when compared to mice on an oleic acid diet. Supplementation of CML mice carrying the T315I mutation (in BCR-ABL) with EPAresulted in a similar effect. Indomethacin blocked the EPA effect and increased the severity of BCR-ABL-induced CML and decreased apoptosis. Δ12-PGJ3 rescued indomethacin-treated BCR-ABL mice and decreased LSCs. Inhibition of hematopoietic-prostaglandin D synthase (H-PGDS) by HQL-79 in EPA-supplemented CML mice also blocked the effect of EPA. In addition, EPA supplementation was effective in a murine model of acute myeloid leukemia. Supplemented mice exhibited a decrease in leukemia burden and a decrease in the LSC colony-forming unit (LSC-CFU). The decrease in LSCs was confirmed through serial transplantation assays in all disease models. The results support a chemopreventive role for EPA in myeloid leukemia, which is dependent on the ability to efficiently convert EPA to endogenous cyclooxygenase-derived prostanoids, including Δ12-PGJ3.

Study Type : Animal Study

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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