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The effect of high dietary eicosapentaenoic acid supplementation in leukemic mice
Author(s) -
Finch Emily,
Kaushal Naveen,
Kudva Avinash,
Gandhi Ujjawal,
Hegde Shailaja,
Whelan Jay,
Paulson Robert,
Prabhu K. Sandeep
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.637.22
Subject(s) - endogeny , eicosapentaenoic acid , pharmacology , haematopoiesis , leukemia , stem cell , apoptosis , prostaglandin e2 , cancer research , medicine , immunology , chemistry , biology , fatty acid , biochemistry , polyunsaturated fatty acid , microbiology and biotechnology
Current chemotherapies for treatment of chronic myelogenous leukemia (CML) do not eliminate leukemic stem cells (LSCs), leading to relapse of the disease. Discovery of alternative therapies to target LSCs is essential for elimination of the disease. We have recently reported on the endogenous production of increased levels of a novel anti‐inflammatory cyclopentenone prostaglandin Δ 12 ‐ prostaglandin J3 (Δ 12 ‐PGJ3), by macrophages cultured with eicosapentaenoic acid (EPA). The levels of EPA used in our studies reflect the doses prescribed by the FDA. To effectively translate these studies, we report here the endogenous production of Δ 12 ‐PGJ3 in mice on high EPA using LC‐MS/MS. Furthermore, we report the effect of high EPA on progression of leukemia and the ability of endogenous metabolites to target the LSCs in a CML model where the hematopoietic stem cells expressing the fusion oncoprotein Bcr‐Abl are transplanted into such mice. Pathways of apoptosis activated by Δ 12 ‐PGJ3 will be discussed. Grant Funding Source : NIH RO1 CA 175576–01