Skip to main content
SpringerLink
Log in

Immune Modulation and Cancer Resistance

Enhancement by ω-3 Fatty Acids

  • Chapter
Wild-Type Food in Health Promotion and Disease Prevention

Abstract

The incidence of cancer of the colon and breast has been steadily increasing in Western countries. The etiology of colon and breast cancer is complex, involving both genetic and environmental factors, including diet. Epidemiological and experimental studies have linked a high dietary intake of ω-6 polyunsaturated fatty acids (PUFAs) such as linoleic acid (C18:2, LA) to an increased risk of cancers of the breast and colon, especially in association with a low intake of ω-3 PUFAs such as docosahexaenoic acid (C22:6, DHA) or eicosapentaenoic acid (EPA) acid. Changes in anticancer immune defenses resulting from this dietary shift in PUFA balance may facilitate cancer progression. Altering the ω-6:ω-3 ratio has been demonstrated to influence immune function in other diseases, however less is known about their effect on immune surveillance during cancer. The biochemical mechanisms whereby decreases in the ω-6:ω-3 ratio of the diet (via increasing DHA and EPA intake) modulate immune function and inhibit tumor growth are not well established but mechanistic studies suggest that this may occur at several sites in the cell. In immune cells, this includes ω-3 PUFA competitively inhibiting arachidonic acid metabolism, altering membrane composition, modifying cell signaling processes and/or changing the expression of genes. In this chapter, we will review the role of the immune system in cancer prevention and promotion, with a focus on evidence from animal and human studies that implicates changes in the level of ω-6 and ω-3 fatty acids in the diet on immune protection from breast and colon cancer. Evidence that points to possible immune mechanisms will also be discussed. Although at the present time it is too early to make any clear recommendations regarding the precise ratio of ω-6:ω-3 PUFA in the diet to impact favorably on anti-cancer defenses, the available evidence presented in this chapter should encourage public health authorities to consider designing primary prevention campaigns to reduce the ω-6/ω-3 ratio of the Western diet by promoting increases in ω-3 PUFA consumption in the population.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst 1981;66:1191–1308.

    CAS  Google Scholar 

  2. Bartsch H, Nair J, Owen RW. Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: emerging evidence for their role as risk modifiers. Carcinogenesis 1999;20:2209–2218.

    Article  CAS  Google Scholar 

  3. Binukumar B, Mathew A. Dietary fat and risk of breast cancer. World J Surg Oncol 2005;3:45.

    Article  Google Scholar 

  4. Mattisson I, Wirfalt E, Johansson U, Gullberg B, Olsson H, Berglund G. Intakes of plant foods, fibre and fat and risk of breast cancer—a prospective study in the Malmo Diet and Cancer cohort. Br J Cancer 2004;90:122–127.

    Article  CAS  Google Scholar 

  5. Boyd NF, Stone J, Vogt KN, Connelly BS, Martin LJ, Minkin S. Dietary fat and breast cancer risk revisited: a meta-analysis of the published literature. Br J Cancer 2003;89:1672–1685.

    Article  CAS  Google Scholar 

  6. Slattery ML, Levin TR, Ma K, Goldgar D, Holubkov R, Edwards S. Family history and colorectal cancer: predictors of risk. Cancer Causes Control 2003;14:879–887.

    Article  CAS  Google Scholar 

  7. Fisher LM. High-fat diet and prostate cancer: the controversial connection. Urol Nurs 2000; 20:205–210.

    CAS  Google Scholar 

  8. Roynette CE, Calder PC, Dupertuis YM, Pichard C. n-3 polyunsaturated fatty acids and colon cancer prevention. Clin Nutr 2004;23:139–151.

    Article  CAS  Google Scholar 

  9. Rose DP, Connolly JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther 1999;83:217–244.

    Article  CAS  Google Scholar 

  10. Hardman WE. Omega-3 fatty acids to augment cancer therapy. J Nutr 2002;132:3508S–3512S.

    CAS  Google Scholar 

  11. Robinson LE, Clandinin MT, Field CJ. R3230AC rat mammary tumor and dietary long-chain (n-3) fatty acids change immune cell composition and function during mitogen activation. J Nutr 2001; 131:2021–2027.

    CAS  Google Scholar 

  12. Robinson LE, Clandinin MT, Field CJ. The role of dietary long-chain n-3 fatty acids in anti-cancer immune defense and R3230AC mammary tumor growth in rats: influence of diet fat composition. Breast Cancer Res Treat 2002;73:145–160.

    Article  CAS  Google Scholar 

  13. Karmali RA, Reichel P, Cohen LA, et al. The effects of dietary ω-3 fatty acids on the DU-145 transplantable human prostatic tumor. Anticancer Res 1987;7:1173–1180.

    CAS  Google Scholar 

  14. Calviello G, Palozza P, Piccioni E, et al. Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: effects on proliferation and apoptosis. Int J Cancer 1998;75:699–705.

    Article  CAS  Google Scholar 

  15. O’Connor TP, Roebuck BD, Peterson FJ, Lokesh B, Kinsella JE, Campbell TC. Effect of dietary omega-3 and omega-6 fatty acids on development of azaserine-induced preneoplastic lesions in rat pancreas. J Natl Cancer Inst 1989;81:858–863.

    Article  CAS  Google Scholar 

  16. Schley PD, Jijon HB, Robinson LE, Field CJ. Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells. Breast Cancer Res Treat 2005;92: 187–195.

    Article  CAS  Google Scholar 

  17. Rose DP, Connolly JM. Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture. Cancer Res 1990;50:7139–7144.

    CAS  Google Scholar 

  18. Clarke RG, Lund EK, Latham P, Pinder AC, Johnson IT. Effect of eicosapentaenoic acid on the proliferation and incidence of apoptosis in the colorectal cell line HT29. Lipids 1999;34:1287–1295.

    Article  CAS  Google Scholar 

  19. Hawkins RA, Sangster K, Arends MJ. Apoptotic death of pancreatic cancer cells induced by polyunsaturated fatty acids varies with double bond number and involves an oxidative mechanism. J Pathol 1998;185:61–70.

    Article  CAS  Google Scholar 

  20. Chiu LCM, Ooi VEC, Wan JMF. Eicosapentaenoic acid modulates cyclin expression and arrests cell cycle progression in human leukemic K-562 cells. Int J Oncol 2001;19:845–849.

    CAS  Google Scholar 

  21. Albino AP, Juan G, Traganos F, et al. Cell cycle arrest and apoptosis of melanoma cells by docosahexaenoic acid: association with decreased pRb phosphorylation. Cancer Res 2000;60:4139–4145.

    CAS  Google Scholar 

  22. Diggle CP. In vitro studies on the relationship between polyunsaturated fatty acids and cancer: tumour or tissue specific effects? Prog Lipid Res 2002;41:240–253.

    Article  CAS  Google Scholar 

  23. Bougnoux P. n-3 polyunsaturated fatty acids and cancer. Curr Opin Clin Nutr Metab Care 1999; 2:121–126.

    Article  CAS  Google Scholar 

  24. Shewchuk LD, Baracos VE, Field CJ. Reduced splenocyte metabolism and immune function in rats implanted with the Morris Hepatoma 7777. Metab 1996;45:848–855.

    Article  CAS  Google Scholar 

  25. Salih HR, Nussler V. Commentary: Immune escape versus tumor tolerance: how do tumors evade immune surveillance? Eur J Med Res 2001;6:323–332.

    CAS  Google Scholar 

  26. Sweeney B, Puri P, Reen DJ. Modulation of immune cell function by polyunsaturated fatty acids. Pediatr Surg Int 2005;21:335–340.

    Article  Google Scholar 

  27. Harbige LS. Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3. Lipids 2003;38:323–341.

    Article  CAS  Google Scholar 

  28. Song C, Li X, Leonard BE, Horrobin DF. Effects of dietary n-3 or n-6 fatty acids on inter-leukin1betainduced anxiety, stress, and inflammatory responses in rats. J Lipid Res 2003;44: 1984–1991.

    Article  CAS  Google Scholar 

  29. Calder PC. Dietary modification of inflammation with lipids. Proc Nutr Soc 2002;61:345–358.

    Article  CAS  Google Scholar 

  30. de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 2006;6:24–37.

    Article  CAS  Google Scholar 

  31. Orange JS, Ballas ZK. Natural killer cells in human health and disease. Clin Immunol 2006; 118: 1–10.

    Article  CAS  Google Scholar 

  32. Foss FM. Immunologic mechanisms of antitumor activity. Semin Oncol 2002;29:5–11.

    Article  CAS  Google Scholar 

  33. Dalerba P, Maccalli C, Casati C, Castelli C, Parmiani G. Immunology and immunotherapy of colorectal cancer. Crit Rev Oncol Hematol 2003;46:33–57.

    Article  Google Scholar 

  34. Allan CP, Turtle CJ, Mainwaring PN, Pyke C, Hart DN. The immune response to breast cancer, and the case for DC immunotherapy. Cytotherapy 2004;6:154–163.

    Article  CAS  Google Scholar 

  35. Andersen MH, Schrama D, Thor SP, Becker JC. Cytotoxic T cells. J Invest Dermatol 2006; 126:32–41.

    Article  CAS  Google Scholar 

  36. Yu JL, Rak JW. Host microenvironment in breast cancer development: inflammatory and immune cells in tumour angiogenesis and arteriogenesis. Breast Cancer Res 2003;5:83–88.

    Article  CAS  Google Scholar 

  37. Cheng F, Gabrilovich D, Sotomayor EM. Immune Tolerance in Breast Cancer. Breast Disease 2004;20:93–103.

    CAS  Google Scholar 

  38. Yaqoob P. Lipids and the immune response: from molecular mechanisms to clinical applications. Curr Opin Clin Nutr Metab Care 2003;6:133–150.

    Article  CAS  Google Scholar 

  39. Mukutmoni-Norris M, Hubbard NE, Erickson KL. Modulation of murine mammary tumor vasculature by dietary n-3 fatty acids in fish oil. Cancer Lett 2000; 150:101–109.

    Article  CAS  Google Scholar 

  40. Rose DP, Connolly JM. Antiangiogenicity of docosahexaenoic acid and its role in the suppression of breast cancer cell growth in nude mice. Int J Oncol 1999;15:1011–1015.

    CAS  Google Scholar 

  41. Calviello G, Di NF, Gragnoli S, et al. n-3 PUFAs reduce VEGF expression in human colon cancer cells modulating the COX-2/PGE2 induced ERK-1 and-2 and HIF-1 alpha induction pathway. Carcinogenesis 2004;25:2303–2310.

    Article  CAS  Google Scholar 

  42. Hansen-Petrik MB, McEntee MF, Chiu CH, Whelan J. Antagonism of arachidonic acid is linked to the antitumorigenic effect of dietary eicosapentaenoic acid in Apc(Min/+) mice. J Nutr 2000; 130: 1153–1158.

    Google Scholar 

  43. Shamsuddin AK. Mucinous colloid adenocarcinoma of colon in Fischer-344 rats. Light microscopy, histochemistry and ultrastructure. J Submicrosc Cytol 1984;16:697–704.

    CAS  Google Scholar 

  44. Shamsuddin AM. Comparative studies of primary, metastatic and transplanted colon adenocarcinomas of Fischer 344 rats. J Submicrosc Cytol 1984; 16:327–339.

    CAS  Google Scholar 

  45. Rao CV, Hirose Y, Indranie C, Reddy BS. Modulation of experimental colon tumorigenesis by types and amounts of dietary fatty acids. Cancer Res 2001;61:1927–1933.

    CAS  Google Scholar 

  46. Hardman WE. (n-3) fatty acids and cancer therapy. J Nutr 2004;134:3427S–3430S.

    CAS  Google Scholar 

  47. Field CJ, Thomson CA, Van Aerde JE, et al. Lower proportion of CD45R0(+) cells and deficient interleukin-10 production by formula-fed infants, compared with human-fed, is corrected with supplementation of long-chain polyunsaturated fatty acids. J Pediatr Gastroenterol Nutr 2000;31:291–299.

    Article  CAS  Google Scholar 

  48. Peterson LD, Jeffery NM, Thies F, Sanderson P, Newsholme EA, Calder PC. Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell-mediated immunity. Lipids 1998;33:171–180.

    Article  CAS  Google Scholar 

  49. Jurkowski JJ, Cave WTJ. Dietary effects of menhaden oil on the growth and membrane lipid composition of rat mammary tumors. J Natl Cancer Inst 1985;74:1145–1150.

    CAS  Google Scholar 

  50. Karmali RA, Donner A, Gobel S, Shimamura T. Effect of n-3 and n-6 fatty acids on 7,12 Dimethylbenz (a) anthracene-induced mammary tumorigenesis. Anticancer Res 1989;9:1161–1168.

    CAS  Google Scholar 

  51. Rose DP, Connolly JM, Rayburn J, Coleman M. Influence of diets containing eicosapentaenoic or docosahexaenoic acid on growth and metastasis of breast cancer cell in nude mice. J Natl Cancer Inst 1995;87:587–592.

    Article  CAS  Google Scholar 

  52. Rose DP. Dietary fatty acids and cancer. Am J Clin Nutr 1997;66:998S–1003S.

    CAS  Google Scholar 

  53. Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A. Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am J Clin Nutr 2004;79:935–945.

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  55. Hwang D. Essential fatty acids and the immune response. FASEB J 1989;3:2052–2061.

    CAS  Google Scholar 

  56. Badawi AF, El Sohemy A, Stephen LL, Ghoshal AK, Archer MC. 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 1998;19:905–910.

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  58. Badawi AF, Badr MZ. Chemoprevention of breast cancer by targeting cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma. Int J Oncol 2002;20:1109–1122.

    CAS  Google Scholar 

  59. Rolland PH, Martin PM, Jacquemier J, Rolland AM, Toga M. Prostaglandin in human breast cancer: Evidence suggesting that an elevated prostaglandin production is a marker of high metastatic potential for neoplastic cells. J Natl Cancer Inst 1980;64:1061–1070.

    CAS  Google Scholar 

  60. Half E, Tang XM, Gwyn K, Sahin A, Wathen K, Sinicrope FA. Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ. Cancer Res 2002;62:1676–1681.

    CAS  Google Scholar 

  61. Harris RE, Beebe-Donk J, Alshafie GA. Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer 2006;6:27.

    Article  CAS  Google Scholar 

  62. Karmali RA, Welt S, Thaler HT, Lefevre F. Prostaglandins in breast cancer: relationship to disease stage and hormone status. Br J Cancer 1983;48:689–696.

    CAS  Google Scholar 

  63. Kibbey WE, Bronn DG, Minton JP. Prostaglandin synthetase and prostaglandin E2 levels in human breast carcinoma. Prostaglandins Med 1979;2:133–139.

    Article  CAS  Google Scholar 

  64. Schrey MP, Patel KV. Prostaglandin E2 production and metabolism in human breast cancer cells and breast fibroblasts. Regulation by inflammatory mediators. Br J Cancer 1995;72:1412–1419.

    CAS  Google Scholar 

  65. Nigam S, Becker R, Rosendahl U, et al. The concentrations of 6-keto-PGF1 alpha and TXB2 in plasma samples from patients with benign and malignant tumours of the breast. Prostaglandins 1985;29:513–528.

    Article  CAS  Google Scholar 

  66. Fulton AM, Ownby HE, Frederick J, Brennan MJ. Relationship of tumor prostaglandin levels to early recurrence in women with primary breast cancer: clinical update. Invasion Metastasis 1986;6: 83–94.

    CAS  Google Scholar 

  67. Basu GD, Pathangey LB, Tinder TL, Gendler SJ, Mukherjee P. Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells. Breast Cancer Res 2005;7:R422–R435.

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  69. Williams CS, Luongo C, Radhika A, et al. Elevated cyclooxygenase-2 levels in Min mouse adenomas. Gastroenterology 1996;111:1134–1140.

    Article  CAS  Google Scholar 

  70. Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996;87:803–809.

    Article  CAS  Google Scholar 

  71. Turini ME, DuBois RN. Cyclooxygenase-2: a therapeutic target. Annu Rev Med 2002;53:35–57.

    Article  CAS  Google Scholar 

  72. Karmali RA, Marsh J, Fuchs C. Effect of omega-3 fatty acids on growth of a rat mammary tumor. J Natl Cancer Inst 1984;73:457–461.

    CAS  Google Scholar 

  73. Abou-El-Ela SH, Prasse KW, Farrell RL, Carroll RW, Wade AE, Bunce OR. Effect of D, L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets. Cancer Res 1989;49:1434–1440.

    CAS  Google Scholar 

  74. Connolly JM, Liu X-H, Rose DP. Effects of dietary menhaden oil, soy, and a cyclooxygenase inhibitor on human breast cancer cell growth and metastasis in nude mice. Nutr Cancer 1997; 29:48–54.

    Article  CAS  Google Scholar 

  75. Connolly JM, Gilhooly EM, Rose DP. Effects of reduced dietary linoleic acid intake, alone or combined with an algal source of docosahexaenoic acid, on MDA-MB-231 breast cancer cell growth and apoptosis in nude mice. Nutr Cancer 1999;35:44–49.

    Article  CAS  Google Scholar 

  76. Fritsche KL, Johnston PV. Effect of dietary α-linolenic acid on growth, metastasis, fatty acid profile and prostaglandin production of two murine mammary adenocarcinomas. J Nutr 1990; 120: 1601–1609.

    CAS  Google Scholar 

  77. Sasaki T, Kobayashi Y, Shimizu J, et al. Effects of dietary n-3-to-n-6 polyunsaturated fatty acid ratio on mammary carcinogenesis in rats. Nutr Cancer 1998;30:137–143.

    CAS  Google Scholar 

  78. Lund EK, Harvey LJ, Ladha S, Clark DC, Johnson IT. Effects of dietary fish oil supplementation on the phospholipid composition and fluidity of cell membranes from human volunteers. Ann Nutr Metab 1999;43:290–300.

    Article  CAS  Google Scholar 

  79. Hashimoto M, Hossain MS, Yamasaki H, Yazawa K, Masumura S. Effect of eicosapentaenoic acid and docosahexaenoic acid on plasma membrane fluidity of aortic endothelial cells. Lipids 1999;34: 1297–1304.

    Article  CAS  Google Scholar 

  80. Jenski LJ, Sturdevant LK, Ehringer WD, Stillwell W. Omega 3 fatty acids increase spontaneous release of cytosolic components from tumor cells. Lipids 1991;26:353–358.

    Article  CAS  Google Scholar 

  81. Stillwell W, Ehringer W, Jenski LJ. Docosahexaenoic acid increases permeability of lipid vesicles and tumor cells. Lipids 1993;28:103–108.

    Article  CAS  Google Scholar 

  82. Grimble RF, Tappia PS. Modulatory influence of unsaturated fatty acids on the biology of tumour necrosis factor-α. Biochem Soc Trans 1995;23:287.

    Google Scholar 

  83. Stubbs CD, Smith AD. The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim Biophys Acta 1984;779: 89–137.

    CAS  Google Scholar 

  84. Carpenter G, Ji Q. Phospholipase C-gamma as a signal-transducing element. Exp Cell Res 1999;253:15–24.

    Article  CAS  Google Scholar 

  85. Hofmann J. Protein kinase C isozymes as potential targets for anticancer therapy. Curr Cancer Drug Targets 2004;4:125–146.

    Article  CAS  Google Scholar 

  86. Ogretmen B, Hannun YA. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer 2004;4:604–616.

    Article  CAS  Google Scholar 

  87. Fowler KH, McMurray DN, Fan Y-Y, Aukema HM, Chapkin RS. Purified dietary n-3 polyunsaturated fatty acids alter diacylglycerol mass and molecular species composition in concanavalin A-stimulated murine splenocytes. Biochim Biophys Acta 1993;1210:89–96.

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  89. McMurray DN, Jolly CA, Chapkin RS. Effects of dietary n-3 fatty acids on T cell activation and T cell receptor-mediated signaling in a murine model. J Infect Dis 2000;182:S103–S107.

    Article  CAS  Google Scholar 

  90. Siddiqui RA, Jenski LJ, Harvey KA, Wiesehan JD, Stillwell W, Zaloga GP. Cell-cycle arrest in Jurkat leukaemic cells: a possible role for docosahexaenoic acid. Biochem J 2003;371:621–629.

    Article  CAS  Google Scholar 

  91. Yaqoob P. Lipids and the immune response. Curr Opin Clin Nutr Metab Care 1998;1:153–161.

    Article  CAS  Google Scholar 

  92. Marignani PA, Sebaldt RJ. The formation of diradylglycerol molecular species in murine peritoneal macrophages varies dose-dependently with dietary purified eicosapentaenoic and docosahexaenoic ethyl esters. J Nutr 1996;126:2738–2745.

    CAS  Google Scholar 

  93. Bell MV, Sargent JR. Effects of the fatty acid composition of phosphatidylserine and diacylglycerol on the in vitro activity of protein kinase C from rat spleen: influences of (n-3) and (n-6) polyunsaturated fatty acids. Comp Biochem Physiol B 1987;86:227–232.

    Article  CAS  Google Scholar 

  94. Hwang D. Fatty acids and immune responses-a new perspective in searching for clues to mechanism. Ann Rev Nutr 2000;20:431–456.

    Article  CAS  Google Scholar 

  95. Sanderson P, Calder PC. Dietary fish oil appears to prevent the activation of phospholipase C-gamma in lymphocytes. Biochim Biophys Acta 1998;1392:300–308.

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  97. Brown DA, London E. Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol 1998;14:111–136.

    Article  CAS  Google Scholar 

  98. Brown DA, Rose JK. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell 1992;68:533–544.

    Article  CAS  Google Scholar 

  99. Simons K, Ikonen E. Functional rafts in cell membranes. Nature 1997;387:569–572.

    Article  CAS  Google Scholar 

  100. Ma DW, Seo J, Switzer KC, et al. n-3 PUFA and membrane microdomains: a new frontier in bioactive lipid research. J Nutr Biochem 2004;15:700–706.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  102. Stulnig TM, Berger M, Sigmund T, Raederstorff D, Stockinger H, Waldhausl W. Polyunsaturated fatty acids inhibit T cell signal transduction by modification of detergent-insoluble membrane domains. J Cell Biol 1998;143:637–644.

    Article  CAS  Google Scholar 

  103. Stulnig TM, Huber J, Leitinger N, et al. Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition. J Biol Chem 2001;276:37,335–37,340.

    Article  CAS  Google Scholar 

  104. Zeyda M, Staffler G, Horejsi V, Waldhausl W, Stulnig TM. LAT displacement from lipid rafts as a molecular mechanism for the inhibition of T cell signaling by polyunsaturated fatty acids. J Biol Chem 2002;277:28,418–28,423.

    Article  CAS  Google Scholar 

  105. Diaz O, Berquand A, Dubois M, et al. The mechanism of docosahexaenoic acid-induced phospholipase D activation in human lymphocytes involves exclusion of the enzyme from lipid rafts. J Biol Chem 2002;277:39,368–39,378.

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  107. Ma DW, Seo J, Davidson LA, et al. n-3 PUFA alter caveolae lipid composition and resident protein localization in mouse colon. FASEB J 2004;18:1040–1042.

    Article  CAS  Google Scholar 

  108. Jump DB, Clarke SD, Thelen A, Liimatta M, Ren B, Badin M. Dietary polyunsaturated fatty acid regulation of gene transcription. Prog Lipid Res 1996;35:227–241.

    Article  CAS  Google Scholar 

  109. Clarke SD, Gasperikova D, Nelson C, Lapillonne A, Heird WC. Fatty acid regulation of gene expression: a genomic explanation for the benefits of the mediterranean diet. Ann NY Acad Sci 2002;967: 283–298.

    Article  CAS  Google Scholar 

  110. Price PT, Nelson CM, Clarke SD. Omega-3 polyunsaturated fatty acid regulation of gene expression. Curr Opin Lipidol 2000;11:3–7.

    Article  CAS  Google Scholar 

  111. Urakazi M, Sugiyama C, Knoell C, et al. Dietary marine lipids suppress the induction of prointerleukin-1β gene transcription. In: Yasugi T, Nakamura H, Soma M, editors. Advances in Polyunsaturated Fatty Acid Research. Elsevier Science Publishers B.V. 1993:83–86.

    Google Scholar 

  112. Jolly CA, McMurray DN, Chapkin RS. Effect of dietary n-3 fatty acids on interleukin-2 and interleukin-2 receptor alpha expression in activated murine lymphocytes. Prostaglandins Leukot Essent Fatty Acids 1998;58:289–293.

    Article  CAS  Google Scholar 

  113. Liu X-H, Rose DP. Suppression of type IV collagenase in MDA-MB-435 human breast cancer cells by eicosapentaenoic acid in vitro and in vivo. Cancer Lett 1995;92:21–26.

    Article  CAS  Google Scholar 

  114. Kliewer SA, Willson TM. The nuclear receptor PPARγ — bigger than fat. Current Opin Genet Dev 1998;8:576–581.

    Article  CAS  Google Scholar 

  115. Kliewer SA, Lehmann JM, Willson TM. Orphan nuclear receptors: shifting endocrinology into reverse. Science 1999;284:757–760.

    Article  CAS  Google Scholar 

  116. Sarraf P, Mueller E, Jones D, et al. Differentiation and reversal of malignant changes in colon cancer through PPARγ. Nat Med 1998;9:1046–1052.

    Article  CAS  Google Scholar 

  117. Krey G, Braissant O, L’Horset F, et al. Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by co-activator-dependent receptor ligand assay. Mol Endocrinol 1997;11:779–791.

    Article  CAS  Google Scholar 

  118. Murakami K, Ide T, Suzuki M, Mochizuki T, Kadowaki T. Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor α. Biochem Biophys Res Commun 1999;260:609–613.

    Article  CAS  Google Scholar 

  119. Xu HE, Lambert MH, Montana VG, et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell 1999;3:397–403.

    Article  CAS  Google Scholar 

  120. Nicholson KM, Anderson NG. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 2002;14:381–395.

    Article  CAS  Google Scholar 

  121. Nakshatri H, Goulet RJ, Jr. NF-kappaB and breast cancer. Curr Probl Cancer 2002;26:282–309.

    Article  Google Scholar 

  122. Moynagh PN. The NF-kappaB pathway. J Cell Sci 2005;118:4589–4592.

    Article  CAS  Google Scholar 

  123. Lee JY, Ye J, Gao Z, et al. Reciprocal modulation of Toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids. J Biol Chem 2003;278:37,041–37,051.

    Article  CAS  Google Scholar 

  124. Lee JY, Zhao L, Youn HS, et al. Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J Biol Chem 2004;279:16,971–16,979.

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  127. Weber C, Erl W, Pietsch A, Danesch U, Weber PC. Docosahexaenoic acid selectively attenuates induction of vascular cell adhesion molecule-1 and subsequent monocytic cell adhesion to human endothelial cells stimulated by tumor necrosis factor-alpha. Arterioscler Thromb Vasc Biol 1995;15: 622–628.

    CAS  Google Scholar 

  128. Esper DH, Harb WA. The cancer cachexia syndrome: a review of metabolic and clinical manifestations. Nutr Clin Pract 2005;20:369–376.

    Google Scholar 

  129. Baracos VE. Hypercatabolism and hypermetabolism in wasting states. Curr Opin Clin Nutr Metab Care 2002;5:237–239.

    Article  Google Scholar 

  130. Fried SK, Zechner R. Cachectin/tumor necrosis factor decreases human adipose meat lipoprotein lipase mRNA levels, synthesis, and activity. J Lipid Res 1989;30:1917–1923.

    CAS  Google Scholar 

  131. Tracey KJ, Wei H, Manogue KR, et al. Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med 1988;167:1211–1227.

    Article  CAS  Google Scholar 

  132. Smith BK, Kluger MJ. Anti-TNF-alpha antibodies normalized body temperature and enhanced food intake in tumor-bearing rats. Am J Physiol 1993;265:R615–R619.

    CAS  Google Scholar 

  133. Socher SH, Martinez D, Craig JB, Kuhn JG, Oliff A. Tumor necrosis factor not detectable in patients with clinical cancer cachexia. J Natl Cancer Inst 1988;80:595–598.

    Article  CAS  Google Scholar 

  134. Falconer JS, Fearon KC, Plester CE, Ross JA, Carter DC. Cytokines, the acute-phase response, and resting energy expenditure in cachectic patients with pancreatic cancer. Ann Surg 1994;219: 325–331.

    Article  CAS  Google Scholar 

  135. Fearon KC, McMillan DC, Preston T, Winstanley FP, Cruickshank AM, Shenkin A. Elevated circulating interleukin-6 is associated with an acute-phase response but reduced fixed hepatic protein synthesis in patients with cancer. Ann Surg 1991;213:26–31.

    Article  CAS  Google Scholar 

  136. Strassmann G, Fong M, Kenney JS, Jacob CO. Evidence for the involvement of interleukin 6 in experimental cancer cachexia. J Clin Invest 1992;89:1681–1684.

    Article  CAS  Google Scholar 

  137. Hellerstein MK, Meydani SN, Meydani M, Wu K, Dinarello CA. Interleukin-1-induced anorexia in the rat. Influence of prostaglandins. J Clin Invest 1989;84:228–235.

    CAS  Google Scholar 

  138. Oldenburg HS, Rogy MA, Lazarus DD, et al. Cachexia and the acute-phase protein response in inflammation are regulated by interleukin-6. Eur J Immunol 1993;23:1889–1894.

    Article  CAS  Google Scholar 

  139. Wigmore SJ, Ross JA, Falconer JS, et al. The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition 1996;12:S27–S30.

    CAS  Google Scholar 

  140. Bruera E, Strasser F, Palmer JL, et al. Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study. J Clin Oncol 2003;21:129–134.

    Article  CAS  Google Scholar 

  141. Fearon KC, Von Meyenfeldt MF, Moses AG, et al. Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut 2003;52:1479–1486.

    Article  CAS  Google Scholar 

  142. Moses AW, Slater C, Preston T, Barber MD, Fearon KC. Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids. Br J Cancer 2004;90:996–1002.

    Article  CAS  Google Scholar 

  143. Barber MD, Fearon KC, Tisdale MJ, McMillan DC, Ross JA. Effect of a fish oil-enriched nutritional supplement on metabolic mediators in patients with pancreatic cancer cachexia. Nutr Cancer 2001; 40:118–124.

    Article  CAS  Google Scholar 

  144. Gogos CA, Ginopoulos P, Salsa B, Apostolidou E, Zoumbos NC, Kalfarentzos F. Dietary omega-3 polyunsaturated fa1tty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial. Cancer 1998;82: 395–402.

    Article  CAS  Google Scholar 

  145. Gogos CA, Ginopoulos P, Zoumbos NC, Apostolidou E, Kalfarentzos F. The effect of dietary omega-3 polyunsaturated fatty acids on T-lymphocyte subsets of patients with solid tumors. Cancer Detect Prev 1995;19:415–417.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada

    Erin M. O’Connell MSc, Patricia D. Schley PhD & Catherine J. Field PhD, RD

Authors
  1. Erin M. O’Connell MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patricia D. Schley PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Catherine J. Field PhD, RD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Belovo S. A., Bastogne, Belgium

    Fabien De Meester PhD (President and CEO) (President and CEO)

  2. Division of Health Promotion Sciences Mel and Enid Zuckerman College of Public Health School of Medicine, University of Arizona, Tucson, AZ

    Ronald Ross Watson PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

O’Connell, E.M., Schley, P.D., Field, C.J. (2008). Immune Modulation and Cancer Resistance. In: De Meester, F., Watson, R.R. (eds) Wild-Type Food in Health Promotion and Disease Prevention. Humana Press. https://doi.org/10.1007/978-1-59745-330-1_20

Download citation

Publish with us

Policies and ethics

Search

Navigation