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Omega-3 Fatty Acids in Cancer Prevention and Control: A Membrane Perspective

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Obesity, Inflammation and Cancer

Part of the book series: Energy Balance and Cancer ((EBAC,volume 7))

Abstract

Long-chain n-3 polyunsaturated fatty acids (PUFA) have been shown to provide health benefits in a number of diseases including several forms of cancer. In this chapter we will discuss in detail some of the prominent mechanisms through which n-3 PUFA and its metabolites are believed to function in the prevention of colon tumorigenesis. At the plasma membrane, n-3 PUFA antagonize the production of inflammatory and procarcinogenic n-6 PUFA (i.e., arachidonic acid)-derived metabolites. Additionally, the highly unsaturated nature of n-3 PUFA impacts cell membrane properties and dynamics thereby altering numerous cellular functions, including intracellular signaling, cell growth, survival, and proliferation. Due to the sterically incompatible relationship between docosahexaenoic acid, sphingolipids, and cholesterol, the major constituents of lipid rafts, n-3 PUFA modulate these crucial membrane microdomains and perturb efficient signal transduction thereby eliciting the same biological effects exploited by some anti-cancer therapies. Moreover, we discuss how alterations in lipid rafts and downstream signaling impact both epithelial cells and the activation of immune cells. This is noteworthy, because chronic inflammation plays a critical role in tumorigenesis. Therefore, we also present an overview regarding the anti-inflammatory and immunomodulatory mechanisms through which n-3 PUFA perturb the tumor microenvironment and downregulate the activation of critical transcription factors and target genes with an established role in cancer development. Finally, we discuss recent evidence suggesting that n-3 PUFA in combination with other dietary bioactive nutrients, such as soluble fiber and curcumin, could be beneficial in cancer prevention. Collectively, we demonstrate that dietary n-3 PUFA have utility in the prevention of cancer development through mechanisms centered at both the molecular, cellular (plasma membrane), and tissue level.

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References

  1. Sargent JR (1997) Fish oils and human diet. Br J Nutr 78(suppl 1):S5–S13

    Article  PubMed  CAS  Google Scholar 

  2. Pawlosky RJ, Hibbeln JR, Novotny JA, Salem N Jr (2001) Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. J Lipid Res 42:1257–1265

    PubMed  CAS  Google Scholar 

  3. Berquin IM, Edwards IJ, Chen YQ (2008) Multi-targeted therapy of cancer by omega-3 fatty acids. Cancer Lett 269:363–377

    Article  PubMed  CAS  Google Scholar 

  4. Caygill CP, Charlett A, Hill MJ (1996) Fat, fish, fish oil and cancer. Br J Cancer 74:159–164

    Article  PubMed  CAS  Google Scholar 

  5. Gerber M (2012) Omega-3 fatty acids and cancers: a systematic update review of epidemiological studies. Br J Nutr 107(suppl 2):S228–S239

    Article  PubMed  CAS  Google Scholar 

  6. Pauwels EK, Kairemo K (2008) Fatty acid facts, part II: role in the prevention of carcinogenesis, or, more fish on the dish? Drug News Perspect 21:504–510

    Article  PubMed  CAS  Google Scholar 

  7. Gerber M (2009) Background review paper on total fat, fatty acid intake and cancers. Ann Nutr Metab 55:140–161

    Article  PubMed  CAS  Google Scholar 

  8. Kim S, Sandler DP, Galanko J, Martin C, Sandler RS (2010) Intake of polyunsaturated fatty acids and distal large bowel cancer risk in whites and African Americans. Am J Epidemiol 171:969–979

    Article  PubMed  Google Scholar 

  9. Kimura Y, Kono S, Toyomura K, Nagano J, Mizoue T, Moore MA, Mibu R, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Yasunami Y, Maekawa T, Takenaka K, Ichimiya H, Imaizumi N (2007) Meat, fish and fat intake in relation to subsite-specific risk of colorectal cancer: The Fukuoka Colorectal Cancer Study. Cancer Sci 98:590–597

    Article  PubMed  CAS  Google Scholar 

  10. Murff HJ, Shrubsole MJ, Cai Q, Smalley WE, Dai Q, Milne GL, Ness RM, Zheng W (2012) Dietary intake of PUFA and colorectal polyp risk. Am J Clin Nutr 95:703–712

    Article  PubMed  CAS  Google Scholar 

  11. Sasazuki S, Inoue M, Iwasaki M, Sawada N, Shimazu T, Yamaji T, Takachi R, Tsugane S (2011) Intake of n-3 and n-6 polyunsaturated fatty acids and development of colorectal cancer by subsite: Japan Public Health Center-based prospective study. Int J Cancer 129:1718–1729

    Article  PubMed  CAS  Google Scholar 

  12. Theodoratou E, McNeill G, Cetnarskyj R, Farrington SM, Tenesa A, Barnetson R, Porteous M, Dunlop M, Campbell H (2007) Dietary fatty acids and colorectal cancer: a case–control study. Am J Epidemiol 166:181–195

    Article  PubMed  Google Scholar 

  13. Hall MN, Chavarro JE, Lee IM, Willett WC, Ma J (2008) A 22-year prospective study of fish, n-3 fatty acid intake, and colorectal cancer risk in men. Cancer Epidemiol Biomarkers Prev 17:1136–1143

    Article  PubMed  CAS  Google Scholar 

  14. Geelen A, Schouten JM, Kamphuis C, Stam BE, Burema J, Renkema JM, Bakker EJ, van’t Veer P, Kampman E (2007) Fish consumption, n-3 fatty acids, and colorectal cancer: a meta-analysis of prospective cohort studies. Am J Epidemiol 166:1116–1125

    Article  PubMed  Google Scholar 

  15. Hall MN, Campos H, Li H, Sesso HD, Stampfer MJ, Willett WC, Ma J (2007) Blood levels of long-chain polyunsaturated fatty acids, aspirin, and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 16:314–321

    Article  PubMed  CAS  Google Scholar 

  16. Kojima M, Wakai K, Tokudome S, Suzuki K, Tamakoshi K, Watanabe Y, Kawado M, Hashimoto S, Hayakawa N, Ozasa K, Toyoshima H, Suzuki S, Ito Y, Tamakoshi A, J.S. Group (2005) Serum levels of polyunsaturated fatty acids and risk of colorectal cancer: a prospective study. Am J Epidemiol 161:462–471

    Article  PubMed  Google Scholar 

  17. Pot GK, Geelen A, van Heijningen EM, Siezen CL, van Kranen HJ, Kampman E (2008) Opposing associations of serum n-3 and n-6 polyunsaturated fatty acids with colorectal adenoma risk: an endoscopy-based case–control study. Int J Cancer 123:1974–1977

    Article  PubMed  CAS  Google Scholar 

  18. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  19. Anti M, Marra G, Armelao F, Bartoli GM, Ficarelli R, Percesepe A, De Vitis I, Maria G, Sofo L, Rapaccini GL et al (1992) Effect of omega-3 fatty acids on rectal mucosal cell proliferation in subjects at risk for colon cancer. Gastroenterology 103:883–891

    PubMed  CAS  Google Scholar 

  20. Bartram HP, Gostner A, Scheppach W, Reddy BS, Rao CV, Dusel G, Richter F, Richter A, Kasper H (1993) Effects of fish oil on rectal cell proliferation, mucosal fatty acids, and prostaglandin E2 release in healthy subjects. Gastroenterology 105:1317–1322

    Article  PubMed  CAS  Google Scholar 

  21. Anti M, Armelao F, Marra G, Percesepe A, Bartoli GM, Palozza P, Parrella P, Canetta C, Gentiloni N, De Vitis I et al (1994) Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Gastroenterology 107:1709–1718

    PubMed  CAS  Google Scholar 

  22. Courtney ED, Matthews S, Finlayson C, Di Pierro D, Belluzzi A, Roda E, Kang JY, Leicester RJ (2007) Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas. Int J Colorectal Dis 22:765–776

    Article  PubMed  CAS  Google Scholar 

  23. West NJ, Clark SK, Phillips RK, Hutchinson JM, Leicester RJ, Belluzzi A, Hull MA (2010) Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut 59:918–925

    Article  PubMed  CAS  Google Scholar 

  24. Stern MC, Butler LM, Corral R, Joshi AD, Yuan JM, Koh WP, Yu MC (2009) Polyunsaturated fatty acids, DNA repair single nucleotide polymorphisms and colorectal cancer in the Singapore Chinese Health Study. J Nutrigenet Nutrigenomics 2:273–279

    Article  PubMed  CAS  Google Scholar 

  25. Hashimoto M, Hossain S, Yamasaki H, Yazawa K, Masumura S (1999) Effects of eicosapentaenoic acid and docosahexaenoic acid on plasma membrane fluidity of aortic endothelial cells. Lipids 34:1297–1304

    Article  PubMed  CAS  Google Scholar 

  26. Stillwell W, Wassall SR (2003) Docosahexaenoic acid: membrane properties of a unique fatty acid. Chem Phys Lipids 126:1–27

    Article  PubMed  CAS  Google Scholar 

  27. Wassall SR, Brzustowicz MR, Shaikh SR, Cherezov V, Caffrey M, Stillwell W (2004) Order from disorder, corralling cholesterol with chaotic lipids. The role of polyunsaturated lipids in membrane raft formation. Chem Phys Lipids 132:79–88

    PubMed  CAS  Google Scholar 

  28. Chapkin RS, Wang N, Fan YY, Lupton JR, Prior IA (2008) Docosahexaenoic acid alters the size and distribution of cell surface microdomains. Biochim Biophys Acta 1778:466–471

    Article  PubMed  CAS  Google Scholar 

  29. Kim W, Fan YY, Barhoumi R, Smith R, McMurray DN, Chapkin RS (2008) n-3 polyunsaturated fatty acids suppress the localization and activation of signaling proteins at the immunological synapse in murine CD4+ T cells by affecting lipid raft formation. J Immunol 181:6236–6243

    PubMed  CAS  Google Scholar 

  30. Rockett BD, Teague H, Harris M, Melton M, Williams J, Wassall SR, Shaikh SR (2012) Fish oil increases raft size and membrane order of B cells accompanied by differential effects on function. J Lipid Res 53:674–685

    Article  PubMed  CAS  Google Scholar 

  31. Shaikh SR, Locascio DS, Soni SP, Wassall SR, Stillwell W (2009) Oleic- and docosahexaenoic acid-containing phosphatidylethanolamines differentially phase separate from sphingomyelin. Biochim Biophys Acta 1788:2421–2426

    Article  PubMed  CAS  Google Scholar 

  32. Pike LJ (2006) Rafts defined: a report on the keystone symposium on lipid rafts and cell ­function. J Lipid Res 47:1597–1598

    Article  PubMed  CAS  Google Scholar 

  33. Pike LJ (2005) Growth factor receptors, lipid rafts and caveolae: an evolving story. Biochim Biophys Acta 1746:260–273

    Article  PubMed  CAS  Google Scholar 

  34. Brown DA, London E (2000) Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J Biol Chem 275:17221–17224

    Article  PubMed  CAS  Google Scholar 

  35. Simons K, Sampaio JL (2011) Membrane organization and lipid rafts. Cold Spring Harb Perspect Biol 3:a004697

    Article  PubMed  CAS  Google Scholar 

  36. Jacobson K, Mouritsen OG, Anderson RG (2007) Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol 9:7–14

    Article  PubMed  CAS  Google Scholar 

  37. Pike LJ (2004) Lipid rafts: heterogeneity on the high seas. Biochem J 378:281–292

    Article  PubMed  CAS  Google Scholar 

  38. Deans JP, Robbins SM, Polyak MJ, Savage JA (1998) Rapid redistribution of CD20 to a low density detergent-insoluble membrane compartment. J Biol Chem 273:344–348

    Article  PubMed  CAS  Google Scholar 

  39. Field KA, Holowka D, Baird B (1997) Compartmentalized activation of the high affinity immunoglobulin E receptor within membrane domains. J Biol Chem 272:4276–4280

    Article  PubMed  CAS  Google Scholar 

  40. Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1:31–39

    Article  PubMed  CAS  Google Scholar 

  41. Smart EJ, Graf GA, McNiven MA, Sessa WC, Engelman JA, Scherer PE, Okamoto T, Lisanti MP (1999) Caveolins, liquid-ordered domains, and signal transduction. Mol Cell Biol 19:7289–7304

    PubMed  CAS  Google Scholar 

  42. Staubach S, Hanisch FG (2011) Lipid rafts: signaling and sorting platforms of cells and their roles in cancer. Expert Rev Proteomics 8:263–277

    Article  PubMed  CAS  Google Scholar 

  43. Hofman EG, Ruonala MO, Bader AN, van den Heuvel D, Voortman J, Roovers RC, Verkleij AJ, Gerritsen HC, van Bergen En Henegouwen PM (2008) EGF induces coalescence of different lipid rafts. J Cell Sci 121:2519–2528

    Article  PubMed  CAS  Google Scholar 

  44. Kono H, Suzuki T, Yamamoto K, Okada M, Yamamoto T, Honda Z (2002) Spatial raft coalescence represents an initial step in Fc gamma R signaling. J Immunol 169:193–203

    PubMed  CAS  Google Scholar 

  45. Patel HH, Murray F, Insel PA (2008) G-protein-coupled receptor-signaling components in membrane raft and caveolae microdomains. Handb Exp Pharmacol 186:167–184

    Article  PubMed  CAS  Google Scholar 

  46. Pike LJ, Han X, Gross RW (2005) Epidermal growth factor receptors are localized to lipid rafts that contain a balance of inner and outer leaflet lipids: a shotgun lipidomics study. J Biol Chem 280:26796–26804

    Article  PubMed  CAS  Google Scholar 

  47. Prior IA, Muncke C, Parton RG, Hancock JF (2003) Direct visualization of Ras proteins in spatially distinct cell surface microdomains. J Cell Biol 160:165–170

    Article  PubMed  CAS  Google Scholar 

  48. George KS, Wu S (2012) Lipid raft: a floating island of death or survival. Toxicol Appl Pharmacol 259:311–319

    Article  PubMed  CAS  Google Scholar 

  49. Alonso MA, Millan J (2001) The role of lipid rafts in signalling and membrane trafficking in T lymphocytes. J Cell Sci 114:3957–3965

    PubMed  CAS  Google Scholar 

  50. Drbal K, Moertelmaier M, Holzhauser C, Muhammad A, Fuertbauer E, Howorka S, Hinterberger M, Stockinger H, Schutz GJ (2007) Single-molecule microscopy reveals heterogeneous dynamics of lipid raft components upon TCR engagement. Int Immunol 19:675–684

    Article  PubMed  CAS  Google Scholar 

  51. Algeciras-Schimnich A, Shen L, Barnhart BC, Murmann AE, Burkhardt JK, Peter ME (2002) Molecular ordering of the initial signaling events of CD95. Mol Cell Biol 22:207–220

    Article  PubMed  CAS  Google Scholar 

  52. Bang B, Gniadecki R, Gajkowska B (2005) Disruption of lipid rafts causes apoptotic cell death in HaCaT keratinocytes. Exp Dermatol 14:266–272

    Article  PubMed  CAS  Google Scholar 

  53. Hazarika P, McCarty MF, Prieto VG, George S, Babu D, Koul D, Bar-Eli M, Duvic M (2004) Up-regulation of Flotillin-2 is associated with melanoma progression and modulates expression of the thrombin receptor protease activated receptor 1. Cancer Res 64:7361–7369

    Article  PubMed  CAS  Google Scholar 

  54. Li YC, Park MJ, Ye SK, Kim CW, Kim YN (2006) Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents. Am J Pathol 168:1107–1118; quiz 1404–1405

    Google Scholar 

  55. Patra SK (2008) Dissecting lipid raft facilitated cell signaling pathways in cancer. Biochim Biophys Acta 1785:182–206

    PubMed  CAS  Google Scholar 

  56. Fedida-Metula S, Feldman B, Koshelev V, Levin-Gromiko U, Voronov E, Fishman D (2012) Lipid rafts couple store-operated Ca2+ entry to constitutive activation of PKB/Akt in a Ca2+/calmodulin-, Src- and PP2A-mediated pathway and promote melanoma tumor growth. Carcinogenesis 33:740–750

    Article  PubMed  CAS  Google Scholar 

  57. Irwin ME, Bohin N, Boerner JL (2011) Src family kinases mediate epidermal growth factor receptor signaling from lipid rafts in breast cancer cells. Cancer Biol Ther 12:718–726

    Article  PubMed  CAS  Google Scholar 

  58. Lasserre R, Guo XJ, Conchonaud F, Hamon Y, Hawchar O, Bernard AM, Soudja SM, Lenne PF, Rigneault H, Olive D, Bismuth G, Nunes JA, Payrastre B, Marguet D, He HT (2008) Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation. Nat Chem Biol 4:538–547

    Article  PubMed  CAS  Google Scholar 

  59. Orr G, Hu D, Ozcelik S, Opresko LK, Wiley HS, Colson SD (2005) Cholesterol dictates the freedom of EGF receptors and HER2 in the plane of the membrane. Biophys J 89:1362–1373

    Article  PubMed  CAS  Google Scholar 

  60. Ringerike T, Blystad FD, Levy FO, Madshus IH, Stang E (2002) Cholesterol is important in control of EGF receptor kinase activity but EGF receptors are not concentrated in caveolae. J Cell Sci 115:1331–1340

    PubMed  CAS  Google Scholar 

  61. Roy UK, Rial NS, Kachel KL, Gerner EW (2008) Activated K-RAS increases polyamine uptake in human colon cancer cells through modulation of caveolar endocytosis. Mol Carcinog 47:538–553

    Article  PubMed  CAS  Google Scholar 

  62. Irwin ME, Mueller KL, Bohin N, Ge Y, Boerner JL (2011) Lipid raft localization of EGFR alters the response of cancer cells to the EGFR tyrosine kinase inhibitor gefitinib. J Cell Physiol 226(9):2316–2328

    Article  PubMed  CAS  Google Scholar 

  63. Lacour S, Hammann A, Grazide S, Lagadic-Gossmann D, Athias A, Sergent O, Laurent G, Gambert P, Solary E, Dimanche-Boitrel MT (2004) Cisplatin-induced CD95 redistribution into membrane lipid rafts of HT29 human colon cancer cells. Cancer Res 64:3593–3598

    Article  PubMed  CAS  Google Scholar 

  64. Rebillard A, Tekpli X, Meurette O, Sergent O, LeMoigne-Muller G, Vernhet L, Gorria M, Chevanne M, Christmann M, Kaina B, Counillon L, Gulbins E, Lagadic-Gossmann D, Dimanche-Boitrel MT (2007) Cisplatin-induced apoptosis involves membrane fluidification via inhibition of NHE1 in human colon cancer cells. Cancer Res 67:7865–7874

    Article  PubMed  CAS  Google Scholar 

  65. Adachi S, Nagao T, Ingolfsson HI, Maxfield FR, Andersen OS, Kopelovich L, Weinstein IB (2007) The inhibitory effect of (−)-epigallocatechin gallate on activation of the epidermal growth factor receptor is associated with altered lipid order in HT29 colon cancer cells. Cancer Res 67:6493–6501

    Article  PubMed  CAS  Google Scholar 

  66. Bacso Z, Bene L, Damjanovich L, Damjanovich S (2002) INF-gamma rearranges membrane topography of MHC-I and ICAM-1 in colon carcinoma cells. Biochem Biophys Res Commun 290:635–640

    Article  PubMed  CAS  Google Scholar 

  67. Ullman TA, Itzkowitz SH (2011) Intestinal inflammation and cancer. Gastroenterology 140:1807–1816

    Article  PubMed  CAS  Google Scholar 

  68. Nicolau DV Jr, Burrage K, Parton RG, Hancock JF (2006) Identifying optimal lipid raft characteristics required to promote nanoscale protein-protein interactions on the plasma membrane. Mol Cell Biol 26:313–323

    Article  PubMed  CAS  Google Scholar 

  69. Corsetto PA, Cremona A, Montorfano G, Jovenitti IE, Orsini F, Arosio P, Rizzo AM (2012) Chemical-physical changes in cell membrane microdomains of breast cancer cells after omega-3 PUFA incorporation. Cell Biochem Biophys 64(1):45–59

    Article  PubMed  CAS  Google Scholar 

  70. Ma DW, Seo J, Davidson LA, Callaway ES, Fan YY, Lupton JR, Chapkin RS (2004) n-3 PUFA alter caveolae lipid composition and resident protein localization in mouse colon. FASEB J 18:1040–1042

    Article  PubMed  CAS  Google Scholar 

  71. Schley PD, Brindley DN, Field CJ (2007) (n-3) PUFA alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells. J Nutr 137:548–553

    PubMed  CAS  Google Scholar 

  72. Ye S, Tan L, Ma J, Shi Q, Li J (2010) Polyunsaturated docosahexaenoic acid suppresses oxidative stress induced endothelial cell calcium influx by altering lipid composition in membrane caveolar rafts. Prostaglandins Leukot Essent Fatty Acids 83:37–43

    Article  PubMed  CAS  Google Scholar 

  73. Poulogiannis G, Luo F, Arends MJ (2012) RAS signalling in the colorectum in health and disease. Cell Commun Adhes 19:1–9

    Article  PubMed  CAS  Google Scholar 

  74. Seo J, Barhoumi R, Johnson AE, Lupton JR, Chapkin RS (2006) Docosahexaenoic acid selectively inhibits plasma membrane targeting of lipidated proteins. FASEB J 20:770–772

    PubMed  CAS  Google Scholar 

  75. Rogers KR, Kikawa KD, Mouradian M, Hernandez K, McKinnon KM, Ahwah SM, Pardini RS (2010) Docosahexaenoic acid alters epidermal growth factor receptor-related signaling by disrupting its lipid raft association. Carcinogenesis 31:1523–1530

    Article  PubMed  CAS  Google Scholar 

  76. Turk HF, Barhoumi R, Chapkin RS (2012) Alteration of EGFR spatiotemporal dynamics suppresses signal transduction. PLoS One 7:e39682

    Article  PubMed  CAS  Google Scholar 

  77. Duraisamy Y, Lambert D, O’Neill CA, Padfield PJ (2007) Differential incorporation of docosahexaenoic acid into distinct cholesterol-rich membrane raft domains. Biochem Biophys Res Commun 360:885–890

    Article  PubMed  CAS  Google Scholar 

  78. Collett ED, Davidson LA, Fan YY, Lupton JR, Chapkin RS (2001) n-6 and n-3 polyunsaturated fatty acids differentially modulate oncogenic Ras activation in colonocytes. Am J Physiol Cell Physiol 280:C1066–C1075

    PubMed  CAS  Google Scholar 

  79. Eisenberg S, Beckett AJ, Prior IA, Dekker FJ, Hedberg C, Waldmann H, Ehrlich M, Henis YI (2011) Raft protein clustering alters N-Ras membrane interactions and activation pattern. Mol Cell Biol 31:3938–3952

    Article  PubMed  CAS  Google Scholar 

  80. Eisenberg S, Henis YI (2008) Interactions of Ras proteins with the plasma membrane and their roles in signaling. Cell Signal 20:31–39

    Article  PubMed  CAS  Google Scholar 

  81. Prior IA, Hancock JF (2012) Ras trafficking, localization and compartmentalized signalling. Semin Cell Dev Biol 23(2):145–153

    Article  PubMed  CAS  Google Scholar 

  82. Sehgal PB, Guo GG, Shah M, Kumar V, Patel K (2002) Cytokine signaling: STATS in plasma membrane rafts. J Biol Chem 277:12067–12074

    Article  PubMed  CAS  Google Scholar 

  83. Monk JM, Kim W, Callaway E, Turk HF, Foreman JE, Peters JM, He W, Weeks B, Alaniz RC, McMurray DN, Chapkin RS (2012) Immunomodulatory action of dietary fish oil and targeted deletion of intestinal epithelial cell PPARdelta in inflammation-induced colon carcinogenesis. Am J Physiol Gastrointest Liver Physiol 302:G153–G167

    Article  PubMed  CAS  Google Scholar 

  84. Ravacci GR, Brentani MM, Tortelli T Jr, Torrinhas RS, Saldanha T, Torres EA, Waitzberg DL (2012) Lipid raft disruption by docosahexaenoic acid induces apoptosis in transformed human mammary luminal epithelial cells harboring HER-2 overexpression. J Nutr Biochem 24:505–515

    Google Scholar 

  85. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444

    Article  PubMed  CAS  Google Scholar 

  86. Chen R, Rabinovitch PS, Crispin DA, Emond MJ, Bronner MP, Brentnall TA (2005) The initiation of colon cancer in a chronic inflammatory setting. Carcinogenesis 26:1513–1519

    Article  PubMed  CAS  Google Scholar 

  87. Ohshima H, Tazawa H, Sylla BS, Sawa T (2005) Prevention of human cancer by modulation of chronic inflammatory processes. Mutat Res 591:110–122

    Article  PubMed  CAS  Google Scholar 

  88. Shishodia S, Aggarwal BB (2004) Nuclear factor-kappaB: a friend or a foe in cancer? Biochem Pharmacol 68:1071–1080

    Article  PubMed  CAS  Google Scholar 

  89. Yan SR, Joseph RR, Rosen K, Reginato MJ, Jackson A, Allaire N, Brugge JS, Jobin C, Stadnyk AW (2005) Activation of NF-kappaB following detachment delays apoptosis in intestinal epithelial cells. Oncogene 24:6482–6491

    PubMed  CAS  Google Scholar 

  90. Janakiram NB, Mohammed A, Rao CV (2011) Role of lipoxins, resolvins, and other bioactive lipids in colon and pancreatic cancer. Cancer Metastasis Rev 30:507–523

    Article  PubMed  CAS  Google Scholar 

  91. Tenesa A, Dunlop MG (2009) New insights into the aetiology of colorectal cancer from genome-wide association studies. Nat Rev Genet 10:353–358

    Article  PubMed  CAS  Google Scholar 

  92. Rustgi AK (2007) The genetics of hereditary colon cancer. Genes Dev 21:2525–2538

    Article  PubMed  CAS  Google Scholar 

  93. Chapkin RS, McMurray DN, Lupton JR (2007) Colon cancer, fatty acids and anti-inflammatory compounds. Curr Opin Gastroenterol 23:48–54

    Article  PubMed  CAS  Google Scholar 

  94. Feagins LA, Souza RF, Spechler SJ (2009) Carcinogenesis in IBD: potential targets for the prevention of colorectal cancer. Nat Rev Gastroenterol Hepatol 6:297–305

    Article  PubMed  CAS  Google Scholar 

  95. Lakatos PL, Lakatos L (2008) Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies. World J Gastroenterol 14:3937–3947

    Article  PubMed  Google Scholar 

  96. Choi J, Yoon SH, Kim JE, Rhee KH, Youn HS, Chung MH (2002) Gene-specific oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa. Int J Cancer 99:485–490

    Article  PubMed  CAS  Google Scholar 

  97. Kraus S, Arber N (2009) Inflammation and colorectal cancer. Curr Opin Pharmacol 9:405–410

    Article  PubMed  CAS  Google Scholar 

  98. Bagga D, Wang L, Farias-Eisner R, Glaspy JA, Reddy ST (2003) Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proc Natl Acad Sci USA 100:1751–1756

    Article  PubMed  CAS  Google Scholar 

  99. Dooper MM, Wassink L, M’Rabet L, Graus YM (2002) The modulatory effects of prostaglandin-E on cytokine production by human peripheral blood mononuclear cells are independent of the prostaglandin subtype. Immunology 107:152–159

    Article  PubMed  CAS  Google Scholar 

  100. Miles EA, Allen E, Calder PC (2002) In vitro effects of eicosanoids derived from different 20-carbon fatty acids on production of monocyte-derived cytokines in human whole blood cultures. Cytokine 20:215–223

    Article  PubMed  CAS  Google Scholar 

  101. Kelley DS, Taylor PC, Nelson GJ, Schmidt PC, Ferretti A, Erickson KL, Yu R, Chandra RK, Mackey BE (1999) Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 34:317–324

    Article  PubMed  CAS  Google Scholar 

  102. Meydani SN, Endres S, Woods MM, Goldin BR, Soo C, Morrill-Labrode A, Dinarello CA, Gorbach SL (1991) Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr 121:547–555

    PubMed  CAS  Google Scholar 

  103. Rees D, Miles EA, Banerjee T, Wells SJ, Roynette CE, Wahle KW, Calder PC (2006) Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr 83:331–342

    PubMed  CAS  Google Scholar 

  104. Trebble TM, Wootton SA, Miles EA, Mullee M, Arden NK, Ballinger AB, Stroud MA, Burdge GC, Calder PC (2003) Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation. Am J Clin Nutr 78:376–382

    PubMed  CAS  Google Scholar 

  105. von Schacky C, Kiefl R, Jendraschak E, Kaminski WE (1993) n-3 fatty acids and cysteinyl-leukotriene formation in humans in vitro, ex vivo, and in vivo. J Lab Clin Med 121:302–309

    Google Scholar 

  106. Maitra A, Ashfaq R, Gunn CR, Rahman A, Yeo CJ, Sohn TA, Cameron JL, Hruban RH, Wilentz RE (2002) Cyclooxygenase 2 expression in pancreatic adenocarcinoma and ­pancreatic intraepithelial neoplasia: an immunohistochemical analysis with automated cellular imaging. Am J Clin Pathol 118:194–201

    Article  PubMed  CAS  Google Scholar 

  107. Rao CV, Reddy BS (2004) NSAIDs and chemoprevention. Curr Cancer Drug Targets 4:29–42

    Article  PubMed  CAS  Google Scholar 

  108. Buchanan FG, DuBois RN (2006) Connecting COX-2 and Wnt in cancer. Cancer Cell 9:6–8

    Article  PubMed  CAS  Google Scholar 

  109. Greenhough A, Wallam CA, Hicks DJ, Moorghen M, Williams AC, Paraskeva C (2010) The proapoptotic BH3-only protein Bim is downregulated in a subset of colorectal cancers and is repressed by antiapoptotic COX-2/PGE(2) signalling in colorectal adenoma cells. Oncogene 29:3398–3410

    Article  PubMed  CAS  Google Scholar 

  110. Park SW, Kim HS, Choi MS, Jeong WJ, Heo DS, Kim KH, Sung MW (2011) The effects of the stromal cell-derived cyclooxygenase-2 metabolite prostaglandin E2 on the proliferation of colon cancer cells. J Pharmacol Exp Ther 336:516–523

    Article  PubMed  CAS  Google Scholar 

  111. Wang D, Dubois RN (2010) The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene 29:781–788

    Article  PubMed  CAS  Google Scholar 

  112. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN (1994) Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107:1183–1188

    PubMed  CAS  Google Scholar 

  113. Kulkarni N, Zang E, Kelloff G, Reddy BS (1992) Effect of the chemopreventive agents piroxicam and D, L-alpha-difluoromethylornithine on intermediate biomarkers of colon carcinogenesis. Carcinogenesis 13:995–1000

    Article  PubMed  CAS  Google Scholar 

  114. Fan YY, Monk JM, Hou TY, Callway E, Vincent L, Weeks B, Yang P, Chapkin RS (2012) Characterization of an arachidonic acid-deficient (Fads1 knockout) mouse model. J Lipid Res 53:1287–1295

    Article  PubMed  CAS  Google Scholar 

  115. Badawi AF, El-Sohemy A, Stephen LL, Ghoshal AK, Archer MC (1998) The effect of dietary n-3 and n-6 polyunsaturated fatty acids on the expression of cyclooxygenase 1 and 2 and levels of p21ras in rat mammary glands. Carcinogenesis 19:905–910

    Article  PubMed  CAS  Google Scholar 

  116. Hamid R, Singh J, Reddy BS, Cohen LA (1999) Inhibition by dietary menhaden oil of cyclooxygenase-1 and -2 in N-nitrosomethylurea-induced rat mammary tumors. Int J Oncol 14:523–528

    PubMed  CAS  Google Scholar 

  117. Ringbom T, Huss U, Stenholm A, Flock S, Skattebol L, Perera P, Bohlin L (2001) Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod 64:745–749

    Article  PubMed  CAS  Google Scholar 

  118. Singh J, Hamid R, Reddy BS (1997) Dietary fat and colon cancer: modulation of cyclooxygenase-2 by types and amount of dietary fat during the postinitiation stage of colon carcinogenesis. Cancer Res 57:3465–3470

    PubMed  CAS  Google Scholar 

  119. Gravaghi C, La Perle KM, Ogrodwski P, Kang JX, Quimby F, Lipkin M, Lamprecht SA (2011) Cox-2 expression, PGE(2) and cytokines production are inhibited by endogenously synthesized n-3 PUFA in inflamed colon of fat-1 mice. J Nutr Biochem 22:360–365

    Article  PubMed  CAS  Google Scholar 

  120. Calviello G, Di Nicuolo F, Gragnoli S, Piccioni E, Serini S, Maggiano N, Tringali G, Navarra P, Ranelletti FO, Palozza P (2004) n-3 PUFA reduce VEGF expression in human colon cancer cells modulating the COX-2/PGE2 induced ERK-1 and -2 and HIF-1alpha induction pathway. Carcinogenesis 25:2303–2310

    Article  PubMed  CAS  Google Scholar 

  121. Habbel P, Weylandt KH, Lichopoj K, Nowak J, Purschke M, Wang JD, He CW, Baumgart DC, Kang JX (2009) Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells. World J Gastroenterol 15:1079–1084

    Article  PubMed  CAS  Google Scholar 

  122. Swamy MV, Cooma I, Patlolla JM, Simi B, Reddy BS, Rao CV (2004) Modulation of cyclooxygenase-2 activities by the combined action of celecoxib and decosahexaenoic acid: novel strategies for colon cancer prevention and treatment. Mol Cancer Ther 3:215–221

    PubMed  CAS  Google Scholar 

  123. Hong S, Gronert K, Devchand PR, Moussignac RL, Serhan CN (2003) Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 278:14677–14687

    Article  PubMed  CAS  Google Scholar 

  124. Serhan CN, Chiang N, Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8:349–361

    Article  PubMed  CAS  Google Scholar 

  125. Serhan CN, Clish CB, Brannon J, Colgan SP, Chiang N, Gronert K (2000) Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med 192:1197–1204

    Article  PubMed  CAS  Google Scholar 

  126. Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG (2004) Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci USA 101:8491–8496

    Article  PubMed  CAS  Google Scholar 

  127. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL (2002) Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 196:1025–1037

    Article  PubMed  CAS  Google Scholar 

  128. Bannenberg G, Arita M, Serhan CN (2007) Endogenous receptor agonists: resolving ­inflammation. ScientificWorldJournal 7:1440–1462

    Article  PubMed  CAS  Google Scholar 

  129. Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN (2005) Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 201:713–722

    Article  PubMed  CAS  Google Scholar 

  130. Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH, Hong S, Serhan CN (2005) Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol 174:4345–4355

    PubMed  CAS  Google Scholar 

  131. Darnell JE Jr (2002) Transcription factors as targets for cancer therapy. Nat Rev Cancer 2:740–749

    Article  PubMed  CAS  Google Scholar 

  132. Karin M, Greten FR (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5:749–759

    Article  PubMed  CAS  Google Scholar 

  133. Kojima M, Morisaki T, Sasaki N, Nakano K, Mibu R, Tanaka M, Katano M (2004) Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression. Anti-cancer Res 24:675–681

    PubMed  CAS  Google Scholar 

  134. Meylan E, Dooley AL, Feldser DM, Shen L, Turk E, Ouyang C, Jacks T (2009) Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma. Nature 462:104–107

    Article  PubMed  CAS  Google Scholar 

  135. Naugler WE, Karin M (2008) NF-kappaB and cancer-identifying targets and mechanisms. Curr Opin Genet Dev 18:19–26

    Article  PubMed  CAS  Google Scholar 

  136. Karin M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441:431–436

    Article  PubMed  CAS  Google Scholar 

  137. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M (2004) IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:285–296

    Article  PubMed  CAS  Google Scholar 

  138. Kim S, Keku TO, Martin C, Galanko J, Woosley JT, Schroeder JC, Satia JA, Halabi S, Sandler RS (2008) Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res 68:323–328

    Article  PubMed  CAS  Google Scholar 

  139. Becker C, Fantini MC, Schramm C, Lehr HA, Wirtz S, Nikolaev A, Burg J, Strand S, Kiesslich R, Huber S, Ito H, Nishimoto N, Yoshizaki K, Kishimoto T, Galle PR, Blessing M, Rose-John S, Neurath MF (2004) TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 21:491–501

    Article  PubMed  CAS  Google Scholar 

  140. Lee JY, Sohn KH, Rhee SH, Hwang D (2001) Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J Biol Chem 276:16683–16689

    Article  PubMed  CAS  Google Scholar 

  141. Novak TE, Babcock TA, Jho DH, Helton WS, Espat NJ (2003) NF-kappa B inhibition by omega-3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol Lung Cell Mol Physiol 284:L84–L89

    PubMed  CAS  Google Scholar 

  142. Weldon SM, Mullen AC, Loscher CE, Hurley LA, Roche HM (2007) Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid. J Nutr Biochem 18:250–258

    Article  PubMed  CAS  Google Scholar 

  143. Zhao Y, Joshi-Barve S, Barve S, Chen LH (2004) Eicosapentaenoic acid prevents LPS-induced TNF-alpha expression by preventing NF-kappaB activation. J Am Coll Nutr 23:71–78

    Article  PubMed  CAS  Google Scholar 

  144. Nowak J, Weylandt KH, Habbel P, Wang J, Dignass A, Glickman JN, Kang JX (2007) Colitis-associated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids. Carcinogenesis 28:1991–1995

    Article  PubMed  CAS  Google Scholar 

  145. Hudert CA, Weylandt KH, Lu Y, Wang J, Hong S, Dignass A, Serhan CN, Kang JX (2006) Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis. Proc Natl Acad Sci USA 103:11276–11281

    Article  PubMed  CAS  Google Scholar 

  146. Fan YY, Ly LH, Barhoumi R, McMurray DN, Chapkin RS (2004) Dietary docosahexaenoic acid suppresses T cell protein kinase C theta lipid raft recruitment and IL-2 production. J Immunol 173:6151–6160

    PubMed  CAS  Google Scholar 

  147. Maziere C, Conte MA, Degonville J, Ali D, Maziere JC (1999) Cellular enrichment with polyunsaturated fatty acids induces an oxidative stress and activates the transcription factors AP1 and NFkappaB. Biochem Biophys Res Commun 265:116–122

    Article  PubMed  CAS  Google Scholar 

  148. Gee JM, Robertson JF, Ellis IO, Nicholson RI (2000) Impact of activation of MAP kinase family members on endocrine response and survival in clinical breast cancer. Eur J Cancer 36(suppl 4):105

    Article  PubMed  Google Scholar 

  149. Neyns B, Teugels E, Bourgain C, Birrerand M, De Greve J (1999) Alteration of jun proto-oncogene status by plasmid transfection affects growth of human ovarian cancer cells. Int J Cancer 82:687–693

    Article  PubMed  CAS  Google Scholar 

  150. Prusty BK, Das BC (2005) Constitutive activation of transcription factor AP-1 in cervical cancer and suppression of human papillomavirus (HPV) transcription and AP-1 activity in HeLa cells by curcumin. Int J Cancer 113:951–960

    Article  PubMed  CAS  Google Scholar 

  151. Wang H, Birkenbach M, Hart J (2000) Expression of Jun family members in human colorectal adenocarcinoma. Carcinogenesis 21:1313–1317

    Article  PubMed  CAS  Google Scholar 

  152. Ashida R, Tominaga K, Sasaki E, Watanabe T, Fujiwara Y, Oshitani N, Higuchi K, Mitsuyama S, Iwao H, Arakawa T (2005) AP-1 and colorectal cancer. Inflammopharmacology 13:113–125

    Article  PubMed  CAS  Google Scholar 

  153. Eferl R, Wagner EF (2003) AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 3:859–868

    Article  PubMed  CAS  Google Scholar 

  154. Jia Q, Ivanov I, Zlatev ZZ, Alaniz RC, Weeks BR, Callaway ES, Goldsby JS, Davidson LA, Fan YY, Zhou L, Lupton JR, McMurray DN, Chapkin RS (2011) Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice. Br J Nutr 106:519–529

    Article  PubMed  CAS  Google Scholar 

  155. Devarajan E, Huang S (2009) STAT3 as a central regulator of tumor metastases. Curr Mol Med 9:626–633

    Article  PubMed  CAS  Google Scholar 

  156. Jarnicki A, Putoczki T, Ernst M (2010) Stat3: linking inflammation to epithelial cancer—more than a “gut” feeling? Cell Div 5:14

    Article  PubMed  CAS  Google Scholar 

  157. Fan YY, Spencer TE, Wang N, Moyer MP, Chapkin RS (2003) Chemopreventive n-3 fatty acids activate RXRalpha in colonocytes. Carcinogenesis 24:1541–1548

    Article  PubMed  CAS  Google Scholar 

  158. Jump DB (2002) The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem 277:8755–8758

    Article  PubMed  CAS  Google Scholar 

  159. Zand H, Rhimipour A, Bakhshayesh M, Shafiee M, Nour Mohammadi I, Salimi S (2007) Involvement of PPAR-gamma and p53 in DHA-induced apoptosis in Reh cells. Mol Cell Biochem 304:71–77

    Article  PubMed  CAS  Google Scholar 

  160. Carter AB, Misyak SA, Hontecillas R, Bassaganya-Riera J (2009) Dietary modulation of inflammation-induced colorectal cancer through PPARgamma. PPAR Res 2009:498352

    PubMed  Google Scholar 

  161. Lefebvre M, Paulweber B, Fajas L, Woods J, McCrary C, Colombel JF, Najib J, Fruchart JC, Datz C, Vidal H, Desreumaux P, Auwerx J (1999) Peroxisome proliferator-activated receptor gamma is induced during differentiation of colon epithelium cells. J Endocrinol 162:331–340

    Article  PubMed  CAS  Google Scholar 

  162. Saez E, Tontonoz P, Nelson MC, Alvarez JG, Ming UT, Baird SM, Thomazy VA, Evans RM (1998) Activators of the nuclear receptor PPARgamma enhance colon polyp formation. Nat Med 4:1058–1061

    Article  PubMed  CAS  Google Scholar 

  163. Voutsadakis IA (2007) Peroxisome proliferator-activated receptor gamma (PPARgamma) and colorectal carcinogenesis. J Cancer Res Clin Oncol 133:917–928

    Article  PubMed  CAS  Google Scholar 

  164. Szanto A, Nagy L (2008) The many faces of PPARgamma: anti-inflammatory by any means? Immunobiology 213:789–803

    Article  PubMed  CAS  Google Scholar 

  165. Thompson EA (2007) PPARgamma physiology and pathology in gastrointestinal epithelial cells. Mol Cells 24:167–176

    PubMed  CAS  Google Scholar 

  166. Karrasch T, Jobin C (2008) NF-kappaB and the intestine: friend or foe? Inflamm Bowel Dis 14:114–124

    Article  PubMed  Google Scholar 

  167. Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, Rose DW, Willson TM, Rosenfeld MG, Glass CK (2005) A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437:759–763

    Article  PubMed  CAS  Google Scholar 

  168. Kong W, Yen JH, Vassiliou E, Adhikary S, Toscano MG, Ganea D (2010) Docosahexaenoic acid prevents dendritic cell maturation and in vitro and in vivo expression of the IL-12 cytokine family. Lipids Health Dis 9:12

    Article  PubMed  CAS  Google Scholar 

  169. Zapata-Gonzalez F, Rueda F, Petriz J, Domingo P, Villarroya F, Diaz-Delfin J, de Madariaga MA, Domingo JC (2008) Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPAR(gamma):RXR heterodimers: comparison with other polyunsaturated fatty acids. J Leukoc Biol 84:1172–1182

    Article  PubMed  CAS  Google Scholar 

  170. Zhao P, Xia HR, Lu GW, Li LX, Meng XL (2004) [The analysis for Raman spectra of Nd:YVO4]. Guang Pu Xue Yu Guang Pu Fen Xi 24:71–73

    PubMed  CAS  Google Scholar 

  171. Forman BM, Chen J, Evans RM (1997) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci USA 94:4312–4317

    Article  PubMed  CAS  Google Scholar 

  172. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM, Lehmann JM (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci USA 94:4318–4323

    Article  PubMed  CAS  Google Scholar 

  173. Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ, Sternbach DD, Lehmann JM, Wisely GB, Willson TM, Kliewer SA, Milburn MV (1999) Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell 3:397–403

    Article  PubMed  CAS  Google Scholar 

  174. Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM, Olefsky JM (2010) GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142:687–698

    Article  PubMed  CAS  Google Scholar 

  175. Im DS (2012) Omega-3 fatty acids in anti-inflammation (pro-resolution) and GPCRs. Prog Lipid Res 51:232–237

    Article  PubMed  CAS  Google Scholar 

  176. Chandramouli A, Mercado-Pimentel ME, Hutchinson A, Gibadulinova A, Olson ER, Dickinson S, Shanas R, Davenport J, Owens J, Bhattacharyya AK, Regan JW, Pastorekova S, Arumugam T, Logsdon CD, Nelson MA (2010) The induction of S100p expression by the prostaglandin E(2) (PGE(2))/EP4 receptor signaling pathway in colon cancer cells. Cancer Biol Ther 10:1056–1066

    Article  PubMed  CAS  Google Scholar 

  177. Cherukuri DP, Chen XB, Goulet AC, Young RN, Han Y, Heimark RL, Regan JW, Meuillet E, Nelson MA (2007) The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells. Exp Cell Res 313:2969–2979

    Article  PubMed  CAS  Google Scholar 

  178. Hawcroft G, Loadman PM, Belluzzi A, Hull MA (2010) Effect of eicosapentaenoic acid on E-type prostaglandin synthesis and EP4 receptor signaling in human colorectal cancer cells. Neoplasia 12:618–627

    PubMed  CAS  Google Scholar 

  179. Arita M, Ohira T, Sun YP, Elangovan S, Chiang N, Serhan CN (2007) Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J Immunol 178:3912–3917

    PubMed  CAS  Google Scholar 

  180. Krishnamoorthy S, Recchiuti A, Chiang N, Yacoubian S, Lee CH, Yang R, Petasis NA, Serhan CN (2010) Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci USA 107:1660–1665

    Article  PubMed  CAS  Google Scholar 

  181. Fan YY, McMurray DN, Ly LH, Chapkin RS (2003) Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts. J Nutr 133:1913–1920

    PubMed  CAS  Google Scholar 

  182. Simons K, Vaz WL (2004) Model systems, lipid rafts, and cell membranes. Annu Rev Biophys Biomol Struct 33:269–295

    Article  PubMed  CAS  Google Scholar 

  183. Zech T, Ejsing CS, Gaus K, de Wet B, Shevchenko A, Simons K, Harder T (2009) Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR signalling. EMBO J 28:466–476

    Article  PubMed  CAS  Google Scholar 

  184. Rentero C, Zech T, Quinn CM, Engelhardt K, Williamson D, Grewal T, Jessup W, Harder T, Gaus K (2008) Functional implications of plasma membrane condensation for T cell activation. PLoS One 3:e2262

    Article  PubMed  CAS  Google Scholar 

  185. Williams JA, Batten SE, Harris M, Rockett BD, Shaikh SR, Stillwell W, Wassall SR (2012) Docosahexaenoic and eicosapentaenoic acids segregate differently between raft and nonraft domains. Biophys J 103:228–237

    Article  PubMed  CAS  Google Scholar 

  186. Kwiatkowska K (2010) One lipid, multiple functions: how various pools of PI(4,5)P(2) are created in the plasma membrane. Cell Mol Life Sci 67:3927–3946

    Article  PubMed  CAS  Google Scholar 

  187. Holub BJ, Kuksis A, Thompson W (1970) Molecular species of mono-, di-, and triphosphoinositides of bovine brain. J Lipid Res 11:558–564

    PubMed  CAS  Google Scholar 

  188. Inoue M, Murase S, Okuyama H (1984) Acyl coenzyme a: phospholipid acyltransferases in porcine platelets discriminate between omega-3 and omega-6 unsaturated fatty acids. Arch Biochem Biophys 231:29–37

    Article  PubMed  CAS  Google Scholar 

  189. Hou TY, Monk JM, Fan YY, Barhoumi R, Chen YQ, Rivera GM, McMurray DN, Chapkin RS (2012) n-3 polyunsaturated fatty acids suppress phosphatidylinositol 4,5-bisphosphate-dependent actin remodelling during CD4+ T-cell activation. Biochem J 443:27–37

    Article  PubMed  CAS  Google Scholar 

  190. Jolly CA, Jiang YH, Chapkin RS, McMurray DN (1997) Dietary (n-3) polyunsaturated fatty acids suppress murine lymphoproliferation, interleukin-2 secretion, and the formation of diacylglycerol and ceramide. J Nutr 127:37–43

    PubMed  CAS  Google Scholar 

  191. Dustin ML, Depoil D (2011) New insights into the T cell synapse from single molecule techniques. Nat Rev Immunol 11:672–684

    Article  PubMed  CAS  Google Scholar 

  192. Tybulewicz VL, Henderson RB (2009) Rho family GTPases and their regulators in lymphocytes. Nat Rev Immunol 9:630–644

    Article  PubMed  CAS  Google Scholar 

  193. Webb Y, Hermida-Matsumoto L, Resh MD (2000) Inhibition of protein palmitoylation, raft localization, and T cell signaling by 2-bromopalmitate and polyunsaturated fatty acids. J Biol Chem 275:261–270

    Article  PubMed  CAS  Google Scholar 

  194. Liang X, Nazarian A, Erdjument-Bromage H, Bornmann W, Tempst P, Resh MD (2001) Heterogeneous fatty acylation of Src family kinases with polyunsaturated fatty acids regulates raft localization and signal transduction. J Biol Chem 276:30987–30994

    Article  PubMed  CAS  Google Scholar 

  195. Zeyda M, Staffler G, Horejsi V, Waldhausl W, Stulnig TM (2002) LAT displacement from lipid rafts as a molecular mechanism for the inhibition of T cell signaling by polyunsaturated fatty acids. J Biol Chem 277:28418–28423

    Article  PubMed  CAS  Google Scholar 

  196. Zeyda M, Szekeres AB, Saemann MD, Geyeregger R, Stockinger H, Zlabinger GJ, Waldhausl W, Stulnig TM (2003) Suppression of T cell signaling by polyunsaturated fatty acids: selectivity in inhibition of mitogen-activated protein kinase and nuclear factor activation. J Immunol 170:6033–6039

    PubMed  CAS  Google Scholar 

  197. Barr VA, Balagopalan L, Barda-Saad M, Polishchuk R, Boukari H, Bunnell SC, Bernot KM, Toda Y, Nossal R, Samelson LE (2006) T-cell antigen receptor-induced signaling complexes: internalization via a cholesterol-dependent endocytic pathway. Traffic 7:1143–1162

    Article  PubMed  CAS  Google Scholar 

  198. Chichili GR, Westmuckett AD, Rodgers W (2010) T cell signal regulation by the actin cytoskeleton. J Biol Chem 285:14737–14746

    Article  PubMed  CAS  Google Scholar 

  199. Hashimoto-Tane A, Yokosuka T, Ishihara C, Sakuma M, Kobayashi W, Saito T (2010) T-cell receptor microclusters critical for T-cell activation are formed independently of lipid raft clustering. Mol Cell Biol 30:3421–3429

    Article  PubMed  CAS  Google Scholar 

  200. Eibert SM, Lee KH, Pipkorn R, Sester U, Wabnitz GH, Giese T, Meuer SC, Samstag Y (2004) Cofilin peptide homologs interfere with immunological synapse formation and T cell activation. Proc Natl Acad Sci USA 101:1957–1962

    Article  PubMed  CAS  Google Scholar 

  201. Faure S, Salazar-Fontana LI, Semichon M, Tybulewicz VL, Bismuth G, Trautmann A, Germain RN, Delon J (2004) ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nat Immunol 5:272–279

    Article  PubMed  CAS  Google Scholar 

  202. Huang Y, Burkhardt JK (2007) T-cell-receptor-dependent actin regulatory mechanisms. J Cell Sci 120:723–730

    Article  PubMed  CAS  Google Scholar 

  203. Nolz JC, Medeiros RB, Mitchell JS, Zhu P, Freedman BD, Shimizu Y, Billadeau DD (2007) WAVE2 regulates high-affinity integrin binding by recruiting vinculin and talin to the immunological synapse. Mol Cell Biol 27:5986–6000

    Article  PubMed  CAS  Google Scholar 

  204. Padrick SB, Cheng HC, Ismail AM, Panchal SC, Doolittle LK, Kim S, Skehan BM, Umetani J, Brautigam CA, Leong JM, Rosen MK (2008) Hierarchical regulation of WASP/WAVE proteins. Mol Cell 32:426–438

    Article  PubMed  CAS  Google Scholar 

  205. Geyeregger R, Zeyda M, Zlabinger GJ, Waldhausl W, Stulnig TM (2005) Polyunsaturated fatty acids interfere with formation of the immunological synapse. J Leukoc Biol 77:680–688

    Article  PubMed  CAS  Google Scholar 

  206. Quann EJ, Liu X, Altan-Bonnet G, Huse M (2011) A cascade of protein kinase C isozymes promotes cytoskeletal polarization in T cells. Nat Immunol 12:647–654

    Article  PubMed  CAS  Google Scholar 

  207. Quintana A, Schwindling C, Wenning AS, Becherer U, Rettig J, Schwarz EC, Hoth M (2007) T cell activation requires mitochondrial translocation to the immunological synapse. Proc Natl Acad Sci USA 104:14418–14423

    Article  PubMed  CAS  Google Scholar 

  208. Schwindling C, Quintana A, Krause E, Hoth M (2010) Mitochondria positioning controls local calcium influx in T cells. J Immunol 184:184–190

    Article  PubMed  CAS  Google Scholar 

  209. Quintana A, Pasche M, Junker C, Al-Ansary D, Rieger H, Kummerow C, Nunez L, Villalobos C, Meraner P, Becherer U, Rettig J, Niemeyer BA, Hoth M (2011) Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activation. EMBO J 30:3895–3912

    Article  PubMed  CAS  Google Scholar 

  210. Muller MR, Rao A (2010) NFAT, immunity and cancer: a transcription factor comes of age. Nat Rev Immunol 10:645–656

    Article  PubMed  CAS  Google Scholar 

  211. Padhan K, Varma R (2010) Immunological synapse: a multi-protein signalling cellular apparatus for controlling gene expression. Immunology 129:322–328

    Article  PubMed  CAS  Google Scholar 

  212. Tuosto L (2011) NF-kappaB family of transcription factors: biochemical players of CD28 co-stimulation. Immunol Lett 135:1–9

    Article  PubMed  CAS  Google Scholar 

  213. Waite JC, Skokos D (2012) Th17 response and inflammatory autoimmune diseases. Int J Inflam 2012:819467

    PubMed  Google Scholar 

  214. Balkwill F, Coussens LM (2004) Cancer: an inflammatory link. Nature 431:405–406

    Article  PubMed  CAS  Google Scholar 

  215. Miyahara Y, Odunsi K, Chen W, Peng G, Matsuzaki J, Wang RF (2008) Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer. Proc Natl Acad Sci USA 105:15505–15510

    Article  PubMed  CAS  Google Scholar 

  216. Su X, Ye J, Hsueh EC, Zhang Y, Hoft DF, Peng G (2010) Tumor microenvironments direct the recruitment and expansion of human Th17 cells. J Immunol 184:1630–1641

    Article  PubMed  CAS  Google Scholar 

  217. Kryczek I, Wei S, Zou L, Altuwaijri S, Szeliga W, Kolls J, Chang A, Zou W (2007) Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment. J Immunol 178:6730–6733

    PubMed  CAS  Google Scholar 

  218. Sfanos KS, Bruno TC, Maris CH, Xu L, Thoburn CJ, DeMarzo AM, Meeker AK, Isaacs WB, Drake CG (2008) Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res 14:3254–3261

    Article  PubMed  CAS  Google Scholar 

  219. Zhang B, Rong G, Wei H, Zhang M, Bi J, Ma L, Xue X, Wei G, Liu X, Fang G (2008) The prevalence of Th17 cells in patients with gastric cancer. Biochem Biophys Res Commun 374:533–537

    Article  PubMed  CAS  Google Scholar 

  220. Kato T, Furumoto H, Ogura T, Onishi Y, Irahara M, Yamano S, Kamada M, Aono T (2001) Expression of IL-17 mRNA in ovarian cancer. Biochem Biophys Res Commun 282:735–738

    Article  PubMed  CAS  Google Scholar 

  221. Steiner GE, Newman ME, Paikl D, Stix U, Memaran-Dagda N, Lee C, Marberger MJ (2003) Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate. Prostate 56:171–182

    Article  PubMed  CAS  Google Scholar 

  222. Numasaki M, Fukushi J, Ono M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MT (2003) Interleukin-17 promotes angiogenesis and tumor growth. Blood 101:2620–2627

    Article  PubMed  CAS  Google Scholar 

  223. Tesmer LA, Lundy SK, Sarkar S, Fox DA (2008) Th17 cells in human disease. Immunol Rev 223:87–113

    Article  PubMed  CAS  Google Scholar 

  224. Maniati E, Soper R, Hagemann T (2010) Up for mischief? IL-17/Th17 in the tumour microenvironment. Oncogene 29:5653–5662

    Article  PubMed  CAS  Google Scholar 

  225. Le Gouvello S, Bastuji-Garin S, Aloulou N, Mansour H, Chaumette MT, Berrehar F, Seikour A, Charachon A, Karoui M, Leroy K, Farcet JP, Sobhani I (2008) High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas. Gut 57:772–779

    Article  PubMed  Google Scholar 

  226. Liu J, Duan Y, Cheng X, Chen X, Xie W, Long H, Lin Z, Zhu B (2011) IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma. Biochem Biophys Res Commun 407:348–354

    Article  PubMed  CAS  Google Scholar 

  227. Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, Berger A, Bruneval P, Fridman WH, Pages F, Galon J (2011) Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res 71:1263–1271

    Article  PubMed  CAS  Google Scholar 

  228. Chae WJ, Gibson TF, Zelterman D, Hao L, Henegariu O, Bothwell AL (2010) Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proc Natl Acad Sci USA 107:5540–5544

    Article  PubMed  CAS  Google Scholar 

  229. Nam JS, Terabe M, Kang MJ, Chae H, Voong N, Yang YA, Laurence A, Michalowska A, Mamura M, Lonning S, Berzofsky JA, Wakefield LM (2008) Transforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17. Cancer Res 68:3915–3923

    Article  PubMed  CAS  Google Scholar 

  230. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, Housseau F, Pardoll DM, Sears CL (2009) A human colonic commensal ­promotes colon tumorigenesis via activation of T helper type 17T cell responses. Nat Med 15:1016–1022

    Article  PubMed  CAS  Google Scholar 

  231. He D, Li H, Yusuf N, Elmets CA, Li J, Mountz JD, Xu H (2010) IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells. J Immunol 184:2281–2288

    Article  PubMed  CAS  Google Scholar 

  232. Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H (2009) IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 206:1457–1464

    Article  PubMed  CAS  Google Scholar 

  233. Hyun YS, Han DS, Lee AR, Eun CS, Youn J, Kim HY (2012) Role of IL-17A in the development of colitis-associated cancer. Carcinogenesis 33:931–936

    Article  PubMed  CAS  Google Scholar 

  234. Durant L, Watford WT, Ramos HL, Laurence A, Vahedi G, Wei L, Takahashi H, Sun HW, Kanno Y, Powrie F, O’Shea JJ (2010) Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 32:605–615

    Article  PubMed  CAS  Google Scholar 

  235. Kortylewski M, Xin H, Kujawski M, Lee H, Liu Y, Harris T, Drake C, Pardoll D, Yu H (2009) Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell 15:114–123

    Article  PubMed  CAS  Google Scholar 

  236. Maloy KJ, Kullberg MC (2008) IL-23 and Th17 cytokines in intestinal homeostasis. Mucosal Immunol 1:339–349

    Article  PubMed  CAS  Google Scholar 

  237. Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, Basham B, McClanahan T, Kastelein RA, Oft M (2006) IL-23 promotes tumour incidence and growth. Nature 442:461–465

    Article  PubMed  CAS  Google Scholar 

  238. Fiaschi T, Chiarugi P (2012) Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. Int J Cell Biol 2012:762825

    PubMed  Google Scholar 

  239. Babior BM (1999) NADPH oxidase: an update. Blood 93:1464–1476

    PubMed  CAS  Google Scholar 

  240. Chiarugi P, Fiaschi T (2007) Redox signalling in anchorage-dependent cell growth. Cell Signal 19:672–682

    Article  PubMed  CAS  Google Scholar 

  241. Storz P (2005) Reactive oxygen species in tumor progression. Front Biosci 10:1881–1896

    Article  PubMed  CAS  Google Scholar 

  242. Chapkin RS, Hong MY, Fan YY, Davidson LA, Sanders LM, Henderson CE, Barhoumi R, Burghardt RC, Turner ND, Lupton JR (2002) Dietary n-3 PUFA alter colonocyte mitochondrial membrane composition and function. Lipids 37:193–199

    Article  PubMed  CAS  Google Scholar 

  243. Hong MY, Chapkin RS, Barhoumi R, Burghardt RC, Turner ND, Henderson CE, Sanders LM, Fan YY, Davidson LA, Murphy ME, Spinka CM, Carroll RJ, Lupton JR (2002) Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytes. Carcinogenesis 23:1919–1925

    Article  PubMed  CAS  Google Scholar 

  244. Costantini P, Jacotot E, Decaudin D, Kroemer G (2000) Mitochondrion as a novel target of anti-cancer chemotherapy. J Natl Cancer Inst 92:1042–1053

    Article  PubMed  CAS  Google Scholar 

  245. Ng Y, Barhoumi R, Tjalkens RB, Fan YY, Kolar S, Wang N, Lupton JR, Chapkin RS (2005) The role of docosahexaenoic acid in mediating mitochondrial membrane lipid oxidation and apoptosis in colonocytes. Carcinogenesis 26:1914–1921

    Article  PubMed  CAS  Google Scholar 

  246. Fan YY, Ran Q, Toyokuni S, Okazaki Y, Callaway ES, Lupton JR, Chapkin RS (2011) Dietary fish oil promotes colonic apoptosis and mitochondrial proton leak in oxidatively stressed mice. Cancer Prev Res 4:1267–1274

    Article  CAS  Google Scholar 

  247. Kolar S, Barhoumi R, Jones CK, Wesley J, Lupton JR, Fan YY, Chapkin RS (2011) Interactive effects of fatty acid and butyrate-induced mitochondrial Ca(2)(+) loading and apoptosis in colonocytes. Cancer 117:5294–5303

    Article  PubMed  CAS  Google Scholar 

  248. Kolar SS, Barhoumi R, Callaway ES, Fan YY, Wang N, Lupton JR, Chapkin RS (2007) Synergy between docosahexaenoic acid and butyrate elicits p53-independent apoptosis via mitochondrial Ca(2+) accumulation in colonocytes. Am J Physiol Gastrointest Liver Physiol 293:G935–G943

    Article  PubMed  CAS  Google Scholar 

  249. Crim KC, Sanders LM, Hong MY, Taddeo SS, Turner ND, Chapkin RS, Lupton JR (2008) Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet. Carcinogenesis 29:1415–1420

    Article  PubMed  CAS  Google Scholar 

  250. Sanders LM, Henderson CE, Hong MY, Barhoumi R, Burghardt RC, Wang N, Spinka CM, Carroll RJ, Turner ND, Chapkin RS, Lupton JR (2004) An increase in reactive oxygen species by dietary fish oil coupled with the attenuation of antioxidant defenses by dietary pectin enhances rat colonocyte apoptosis. J Nutr 134:3233–3238

    PubMed  CAS  Google Scholar 

  251. Saw CL, Huang Y, Kong AN (2010) Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid. Biochem Pharmacol 79:421–430

    Article  PubMed  CAS  Google Scholar 

  252. Kim W, Fan YY, Smith R, Patil B, Jayaprakasha GK, McMurray DN, Chapkin RS (2009) Dietary curcumin and limonin suppress CD4+ T-cell proliferation and interleukin-2 production in mice. J Nutr 139:1042–1048

    Article  PubMed  CAS  Google Scholar 

  253. Simopoulos AP (1991) Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr 54:438–463

    PubMed  CAS  Google Scholar 

  254. Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR (2011) Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr 93:950–962

    Article  PubMed  CAS  Google Scholar 

  255. Russo GL (2009) Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention. Biochem Pharmacol 77:937–946

    Article  PubMed  CAS  Google Scholar 

  256. Simopoulos AP (2002) The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 56:365–379

    Article  PubMed  CAS  Google Scholar 

  257. Colditz GA, Wolin KY, Gehlert S (2012) Applying what we know to accelerate cancer prevention. Sci Transl Med 4:127rv124

    Article  Google Scholar 

  258. Moses H III, Dorsey ER, Matheson DH, Thier SO (2005) Financial anatomy of biomedical research. JAMA 294:1333–1342

    Article  PubMed  CAS  Google Scholar 

  259. Kaiser J (2012) Profile: Bert Vogelstein. Cancer genetics with an edge. Science 337:282–284

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by National Institute of Health grants CA59034, CA129444, CA168312 and by USDA 2010-34402-20875 and the Cancer Prevention and Research Institute of Texas grant RP100473.

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Authors and Affiliations

  1. Program in Integrative Nutrition and Complex Diseases and the Center for Environmental and Rural Health Texas A&M University, College Station, TX, 77843, USA

    Harmony F. Turk Ph.D., Jennifer M. Monk Ph.D. & Tim Y. Hou B.S.

  2. Kleberg Center, Texas A&M University, Room 218B, TAMU 2253, College Station, TX, 77843-2253, USA

    Robert S. Chapkin Ph.D.

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  1. Harmony F. Turk Ph.D.
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  3. Tim Y. Hou B.S.
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Correspondence to Robert S. Chapkin Ph.D. .

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  1. , Department of Medicine, Weill Cornell Medical College, 525 E. 68th St. Room F-206, New York, 10065, New York, USA

    Andrew J. Dannenberg

  2. School of Medicine, Center for Science, Health & Society, Case Western Reserve University, Euclid Ave. 10900, Cleveland, 44106, Ohio, USA

    Nathan A. Berger

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Turk, H.F., Monk, J.M., Hou, T.Y., Chapkin, R.S. (2013). Omega-3 Fatty Acids in Cancer Prevention and Control: A Membrane Perspective. In: Dannenberg, A., Berger, N. (eds) Obesity, Inflammation and Cancer. Energy Balance and Cancer, vol 7. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6819-6_12

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