Prostate cancer incidence is reduced in men who consume increased amounts of n-3 fatty acids (versus n-6 fatty acids) and this observation has led to the suggestion that these fatty acids are useful dietary supplements to prevent cancer and reduce its recurrence. Since both the n-3 and n-6 are essential fatty acids, their relative levels in tissues are totally controlled by diet. The membranes of mammalian cells are composed of an array of phospholipid species that are now recognized to function as a diverse source of lipid mediators. These mediators function as both intercellular and intracellular signals and are key components of signaling cascades. Arachidonic acid (AA),an n-6 fatty acid, is the major precursor for prostaglandins and leukotrienes in people consuming a typical """"""""Western diet"""""""". However, when the diet is enriched in n-3 fatty acids the synthesis of lipid mediators is markedly altered. The levels of ether-linked phospholipids vary greatly among cells;but, in a number of cells they are known to serve as an important reservoir of AA and as a precursor of platelet activating factor (PAF), one of the most active mediators known. When the diet is rich in n-3 fatty acids the levels of AA in the ether-linked lipids is reduced. We hypothesize that supplementation of cells with n-3 fatty acids will result in lipid alterations that decrease PAF precursors and thus PAF synthesis.
Our specific aims are: (1) to determine the effect of n-3 fatty acid supplementation on the synthesis of PAF and eicosanoids;(2) to determine if n-3 fatty acid-altered PAF synthesis alters the growth of prostate cancer cells in vitro;and (3) to determine if n-3 fatty acid-altered synthesis of PAF and eicosanoids alters the growth of prostate cancer cells in vivo. The proposed studies promise to advance our understanding of the role of n-3 fatty acids in tumor cells and could lead to new therapeutic approaches and targets.
| Suburu, Janel; Shi, Lihong; Wu, Jiansheng et al. (2014) Fatty acid synthase is required for mammary gland development and milk production during lactation. Am J Physiol Endocrinol Metab 306:E1132-43 |
| Wang, Mingxuan; Chen, Haiqin; Gu, Zhennan et al. (2013) ?3 fatty acid desaturases from microorganisms: structure, function, evolution, and biotechnological use. Appl Microbiol Biotechnol 97:10255-62 |
| O'Flaherty, Joseph T; Wooten, Rhonda E; Samuel, Michael P et al. (2013) Fatty acid metabolites in rapidly proliferating breast cancer. PLoS One 8:e63076 |
| Suburu, Janel; Gu, Zhennan; Chen, Haiqin et al. (2013) Fatty acid metabolism: Implications for diet, genetic variation, and disease. Food Biosci 4:1-12 |
| Chen, Haiqin; Gu, Zhennan; Zhang, Hao et al. (2013) Expression and purification of integral membrane fatty acid desaturases. PLoS One 8:e58139 |
| Chen, Yong Q (2013) Cancer and Metastasis Reviews. Introduction. Cancer Metastasis Rev 32:3-4 |
| Gu, Zhennan; Wu, Jiansheng; Wang, Shihua et al. (2013) Polyunsaturated fatty acids affect the localization and signaling of PIP3/AKT in prostate cancer cells. Carcinogenesis 34:1968-75 |
| Hu, Yunping; Sun, Haiguo; O'Flaherty, Joseph T et al. (2013) 15-Lipoxygenase-1-mediated metabolism of docosahexaenoic acid is required for syndecan-1 signaling and apoptosis in prostate cancer cells. Carcinogenesis 34:176-82 |
| Suburu, Janel; Chen, Yong Q (2012) Lipids and prostate cancer. Prostaglandins Other Lipid Mediat 98:1-10 |
| Conley-LaComb, M Katie; Huang, Wei; Wang, Shihua et al. (2012) PTEN regulates PDGF ligand switch for ?-PDGFR signaling in prostate cancer. Am J Pathol 180:1017-27 |
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