Skip to main content
SpringerLink
Log in

Immunomodulation by Fish Oil Derived Polyunsaturated Fatty Acids in Cancer

  • Chapter
  • First Online:
Dietary Components and Immune Function

Part of the book series: Nutrition and Health ((NH))

  • 2095 Accesses

Key Points

Omega-3 fatty acids (ω-3 FA) have shown their efficacy in the treatment of chronic and acute diseases due to their pleiotropic effects on cell signaling pathways linked to inflammation, angiogenesis, and cell cycle progression. In a variety of human cancer cell lines derived from colonic, pancreatic, prostate, and breast cancer, omega-3 fatty acids attenuated growth and induced apoptosis. Recent findings likewise indicate that ω3-FA act synergistically with chemotherapeutic agents and may also be used to enhance tumor radiosensitivity. This chapter sheds light on all relevant known pathway systems today taking also in account recent epidemiologic studies on the nutritional role of ω-3 FA in the prevention of cancer development.

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 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

References

  1. Uniting to defeat cancer. International Union against cancer, Annual report 2007

    Google Scholar 

  2. Caygill CP, Charlett A, Hill MJ (1996) Fat, fish, fish oil and cancer. Br J Cancer 74(1):159–164

    Article  PubMed  CAS  Google Scholar 

  3. Hardman WE (2002) Omega-3 fatty acids to augment cancer therapy. J Nutr 132(11 Suppl): 3508S–3512S

    PubMed  CAS  Google Scholar 

  4. Fearon KCH (2002) The anticancer and anticachectic effects of n-3 fatty acids. Clin Nutr 21(Suppl 2):69–73

    Google Scholar 

  5. MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, Lim Y-W, Traina SB, Hilton L, Garland R, Morton SC (2006) Effects of omega-3 fatty acids on cancer risk: a systematic review. JAMA 295(4):403–415

    Article  PubMed  CAS  Google Scholar 

  6. Hyman BT, Spector AA (1981) Accumulation of N-3 polyunsaturated fatty acids cultured human Y79 retinoblastoma cells. J Neurochem 37(1):60–69

    Article  PubMed  CAS  Google Scholar 

  7. Spector AA, Steinberg D (1967) Turnover and utilization of esterified fatty acids in Ehrlich ascites tumor cells. J Biol Chem 242(13):3057–3062

    PubMed  CAS  Google Scholar 

  8. Burns CP, Spector AA (1987) Membrane fatty acid modification in tumor cells: a potential therapeutic adjunct. Lipids 22(3):178–184

    Article  PubMed  CAS  Google Scholar 

  9. Sauer LA, Dauchy RT, Blask DE, Krause JA, Davidson LK, Dauchy EM (2005) Eicosapentaenoic acid suppresses cell proliferation in MCF-7 human breast cancer xenografts in nude rats via a pertussis toxin-sensitive signal transduction pathway. J Nutr 135(9):2124–2129

    PubMed  CAS  Google Scholar 

  10. Sauer LA, Dauchy RT, Blask DE (2001) Polyunsaturated fatty acids, melatonin, and cancer prevention. Biochem Pharmacol 61(12):1455–1462

    Article  PubMed  CAS  Google Scholar 

  11. Breil I, Koch T, Heller A, Schlotzer E, Grunert A, van Ackern K et al (1996) Alteration of n-3 fatty acid composition in lung tissue after short-term infusion of fish oil emulsion attenuates inflammatory vascular reaction. Crit Care Med 24(11):1893–1902

    Article  PubMed  CAS  Google Scholar 

  12. Wu C, Butz S, Ying Y, Anderson RGW (1997) Tyrosine kinase receptors concentrated in caveolae-like domains from neuronal plasma membrane. J Biol Chem 272:3554–3559

    Article  PubMed  CAS  Google Scholar 

  13. Sengupta P, Baird B, Holowka D. Lipid rafts, fluid/fluid phase separation, and their relevance to plasma membrane structure and function. Semin Cell Dev Biol 2007; doi:10.1016/semcdb2007.07.010

    Google Scholar 

  14. Hanada K, Nishijima M, Akamatsu Y, Pagano RE (1995) Both sphingolipids and cholesterol participate in the detergent insolubility of alkaline phosphatase, a glycosylphosphatidylinositol-anchored protein, in mammalian membranes. J Biol Chem 270:6254–6260

    Article  PubMed  CAS  Google Scholar 

  15. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572

    Article  PubMed  CAS  Google Scholar 

  16. Melkonian KA, Ostermeyer AG, Chen JZ, Roth MG, Brown DA (1999) Role of lipid modifications in targeting proteins to detergent-resistant membrane rafts. J Biol Chem 274:3910–3917

    Article  PubMed  CAS  Google Scholar 

  17. Resh MD (1999) Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim Biophys Acta 1451:1–16

    Article  PubMed  CAS  Google Scholar 

  18. Ahmed SN, Brown DA, London E (1997) On the origin of sphingolipid/cholesterol-rich detergent-insoluble cell membranes: physiological concentrations of cholesterol and sphingolipid induce ­formation of a detergent-insoluble, liquid-ordered lipid phase in model membranes. Biochemistry 36:10944–10953

    Article  PubMed  CAS  Google Scholar 

  19. Robinson DR, Xu LL, Knoell CT, Tateno S, Olesiak W (1993) Modification of spleen phospholipids fatty acid composition by dietary fish oil and by n-3 fatty acid ethyl esters. J Lipid Res 34:1423–1434

    PubMed  CAS  Google Scholar 

  20. Mitchell DC, Litman BJ (1998) Molecular order and dynamics in bilayers consisting of highly polyunsaturated phospholipids. Biophys J 74:879–891

    Article  PubMed  CAS  Google Scholar 

  21. Huster D, Arnold K, Gawrisch K (1998) Influence of docosahexaenoic acid and cholesterol on lateral lipid organization in phospholipids mixtures. Biochemistry 37:17299–17308

    Article  PubMed  CAS  Google Scholar 

  22. Hashimoto M, Hossain S, Tanabe Y, Shido O (2005) Effects of aging on the relation of adenyl purine release with plasma membrane fluidity of arterial endothelial cells. Prostaglandins Leukot Essent Fatty Acids 73:475–483

    Article  PubMed  CAS  Google Scholar 

  23. Stulnig TM, Huber J, Leitinger N, Imre EM, Angelisová P, Nowotny P, Waldhäusl W (2001) Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition. J Biol Chem 276:37335–37340

    Article  PubMed  CAS  Google Scholar 

  24. Armstrong VT, Brzustowicz MR, Wassall SR, Jenski LJ, Stillwell W (2003) Rapid flip-flop in polyunsaturated (docosahexaenoate) phospholipid membranes. Arch Biochem Biophys 414:74–82

    Article  PubMed  CAS  Google Scholar 

  25. Heller A, Koch T, Schmeck J (1998) van Ackern K:Lipid mediators in inflammatory disorders. Drugs 55(4):487–496

    Article  PubMed  CAS  Google Scholar 

  26. Serhan CN (2007) Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol 25:101–137

    Article  PubMed  CAS  Google Scholar 

  27. Levy BD, Clish CB, Schmidt B, Gronert K, Serhan CN (2001) Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol 2(7):612–619

    Article  PubMed  CAS  Google Scholar 

  28. 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(8):1197–1204

    Article  PubMed  CAS  Google Scholar 

  29. Serhan CN, Gotlinger K, Hong S, Lu Y, Siegelman J, Baer T, Yang R, Colgan SP, Petasis NA (2006) Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol 176(3):1848–1859

    PubMed  CAS  Google Scholar 

  30. 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 

  31. Qureshi N, Takayama K, Kurtz R (1991) Diphosphoryl lipid A obtained from the nontoxic lipopolysaccharide of Rhodopseudomonas sphaeroides is an endotoxin antagonist in mice. Infect Immun 59:441–444

    PubMed  CAS  Google Scholar 

  32. Lee JY, Ye J, Gao Z, Youn HS, Lee WH, WH ZL, Sizemore N, Hwang DH (2003) 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 278:37041–37051

    Article  PubMed  CAS  Google Scholar 

  33. Da Silva CJ, Soldau K, Christen U, Tobias PS, Ulevitch RJ (2001) Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. J Biol Chem 276:21129–21135

    Article  Google Scholar 

  34. Lee JY, Zhao L, Youn HS, Weatherill AR, Tapping R, Feng L, Lee WH, Fitzgerald KA, Hwang DH (2004) Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J Biol Chem 279:16971–16979

    Article  PubMed  CAS  Google Scholar 

  35. Chu AJ, Walton MA, Prasad JK, Seto A (1999) Blockade by polyunsaturated n-3 fatty acids of ­endotoxin-induced monocytic issue factor activation is mediated by the depressed receptor expression of THP-1 cells. Surg Res 87:217–224

    Article  CAS  Google Scholar 

  36. Shenoy-Scaria AM, Dietzen DJ, Kwong J, Link DC, Lublin DM (1994) Cysteine3 of Src family protein tyrosine kinase determines palmitoylation and localization in caveolae. J Cell Biol 126:353–363

    Article  PubMed  CAS  Google Scholar 

  37. Zhang W, Trible RP, Samelson LE (1998) LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation. Immunity 9:239–246

    Article  PubMed  CAS  Google Scholar 

  38. Li Q, Wang M, Tan L, Wang C, Ma J, Li N, Li Y, Xu G (2005) Li J (Docosahexaenic acid changes lipid composition and interleukin-2 receptor signaling in membrane rafts. J Lipid Res 46:1904–1913

    Article  PubMed  CAS  Google Scholar 

  39. Zhang J, Kim W, Zhou L, Wang N, Ly LH, McMurray DN, Chapkin RS (2006) Dietary fish oil inhibits antigen-specific muine Th1 cell development by suppression of clonal expansion. J Nutr 136:2391–2398

    PubMed  CAS  Google Scholar 

  40. Pompos LJ, Fritsche KL (2002) Antigen-driven murine CD4+ T lymphocyte proliferation and interleukin-2 production are diminished by dietary (n) polyunsaturated fatty acids. J Nutr 132:3293–3300

    PubMed  CAS  Google Scholar 

  41. Anderson MJ, Fritsche KL (2004) Dietary polyunsaturated fatty acids modulate in vivo, antigen-driven CD4+ T-cell proliferation in mice. J Nutr 134:1978–1983

    PubMed  CAS  Google Scholar 

  42. Peterson LD, Jeffrey NM, Thies F, Sanderson P, Newsholme EA, Calder CA (1998) 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 33:171–180

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  44. Switzer KC, Fan YY, Wang N, McMurray DN, Chapkin RS (2004) Dietary n-3 polyunsaturated fatty acids promote activaito-induced cell death in Th1-polarized murine CD4+ T-cells. J Lipid Res 45:1482–1492

    Article  PubMed  CAS  Google Scholar 

  45. Pascale AW, Ehringer WD, Stillwell W, Sturdevant LK, Jenski LJ (1993) Omega-3 fatty acid modification of membrane structure and function. II. Alteration by docosahexaenoic acid of tumor cell sensitivity to immune cytolysis. Nutr Cancer 19:147–157

    Article  PubMed  CAS  Google Scholar 

  46. Hughes DA, Pinder AC (1997) N-3 Polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes and inhibit antigen presentation in vitro. Clin Exp Immunol 110:516–523

    Article  PubMed  CAS  Google Scholar 

  47. Hughes DA, Pinder AC, Piper Z, Johnson IT, Lund EK (1996) Fish oil supplementation inhibits the expression of major histocompatibility complex class II molecules and adhesion molecules on human monocytes. Am J Clin Nutr 63:267–272

    PubMed  CAS  Google Scholar 

  48. Zeyda M, Saemann MD, Stuhlmeier KM, Mascher DG, Nowotny PN, Zlabinger GJ, Waldhäusl W, Stulnig TM (2005) Polyunsaturated fatty acids block dendritic cell activation and function independently of NF-κB activation. J Biol Chem 280:14293–14301

    Article  PubMed  CAS  Google Scholar 

  49. Erickson BL, Howard AD, Chakrabarti R, Hubbard NE (1997) Alteration of platelet actvating factor-induced macrophage tumoricidal response, IA expression, and signal transduction by n-3 fatty acids. Adv Exp Med Biol 407:371–378

    PubMed  CAS  Google Scholar 

  50. Thies F, Miles EA, Nebe-von-Caron G, Powell JR, Hurst TL, Newsholme EA, Calder PC (2001) Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults. Lipids 36:1183–1193

    Article  PubMed  CAS  Google Scholar 

  51. Kelley DS, Taylor PC, Nelson GJ, Mackey BE (1998) Dietary docosahexaenoic acid and immnocompetence in young healthy men. Lipids 33:559–566

    Article  PubMed  CAS  Google Scholar 

  52. Weiss G, Meyer F, Matthies B, Pross M, Koenig W, Lippert H (2002) Immunomodulation by perioperative administration of n-3 fatty acids. Br J Nutr 87(Suppl 1):S89–S94

    Article  PubMed  CAS  Google Scholar 

  53. Lim HY, Joo HJ, Choi JH, Yi JW, Yang MS, Cho DY, Kim Nam DK, Lee KB, Him HC (2000) Increased expression of cyclooxygenase-2 protein in human gastric carcinoma. Clin Cancer Res 6(2):519–525

    PubMed  CAS  Google Scholar 

  54. Sheehan KM, Sheehan K, O’Donoghue DP, MacSweeeny F, Conroy RM, Fidzgerald DJ, Murray FE (1999) The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 282(13):1254–1257

    Article  PubMed  CAS  Google Scholar 

  55. Edelman MJ, Watson D, Wang X, Morrison C, Kratzke RA, Jewell S (2008) Hodgson, L, et al. Eicosanoid modulation in advanced lung cancer: cyclooxygenase-2 expression is a positive predictive factor for celecoxib + chemotherapy – Cancer and Leukemia Group B Trial 30203. J Clin Oncol 26(6):848–855

    Article  PubMed  CAS  Google Scholar 

  56. Ferrandina G, Lauriola L, Distefano MG, Zannoni GF, Gessi M, Legge F, Maggiano N, Mancuso S, Capelli A, Scambia G, Ranelletti FO (2002) Increased cyclooxygenase-2 expression is associated with chemotherapy resistance and poor survival in cervical cancer patients. J Clin Oncol 20(4):973–981

    Article  PubMed  CAS  Google Scholar 

  57. Kokawa A, Kondo H, Gotoda T, Ono H, Saito D, Nakadaira S, Kosuge T, Yoshida S (2001) Increased expression of cyclooxygenase-2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors. Cancer (Phila) 91(2):333–338

    Article  CAS  Google Scholar 

  58. Shappell SB, Manning S, Boeglin WE, Guan YF, Roberts RL, Davis L, Olson SJ, Jack GS, Coffey CS, Wheller TM (2001) Alterations in lipoxygenase and cyclooxygenase-2 catalytic activity and mRNA expression in prostate carcinoma. Neoplasia 3(4):287–303

    Article  PubMed  CAS  Google Scholar 

  59. Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ, Seibert K (2000) Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 60(5):1306–1311

    PubMed  CAS  Google Scholar 

  60. Liu CH, Chang S-H, Narko K, Trifan OC, Wu M-T, Smith E, Haudenschild C, Lane TF, Hla T (2001) Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 276(21):18563–18569

    Article  PubMed  CAS  Google Scholar 

  61. Repasky GA, Zhou Y, Morita S, Der CJ (2007) Ras-mediated intestinal epithelial cell transformation requires cyclooxygenase-2-induced prostaglandin E2 signaling. Mol Carcinog 46(12):958–970

    Article  PubMed  CAS  Google Scholar 

  62. Calviello G, Di Nicuolo F, Gragnoli S, Piccioni E, Serini S, Maggiano N, Tringali G, Navarra P, Ranelletti FO, Palozza P (2004) n-3 PUFAs 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(12):2303–2310

    Article  PubMed  CAS  Google Scholar 

  63. Wang X, Klein RD (2007) Prostaglandin E2 induces vascular endothelial growth factor secretion in prostate cancer cells through EP2 receptor-mediated cAMP pathway. Mol Carcinog 46(11):912–923

    Article  PubMed  CAS  Google Scholar 

  64. Takahashi Y, Kitaday Y, Bucana CD, Cleary KR, Ellis LM (1995) Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 55(18):3964–3968

    PubMed  CAS  Google Scholar 

  65. Hong MY, Chapkin RS, Davidson LA, Turner ND, Morris JS, Carroll RJ, Lupton JR (2003) Fish oil enhances targeted apoptosis during colon tumor initiation in part by downregulating Bcl-2. Nutr Cancer 46(1):44–51

    Article  PubMed  CAS  Google Scholar 

  66. George RJ, Sturmoski MA, Anant S, Houchen CW (2007) EP4 mediates PGE2 dependent cell survival through the PI3 kinase/AKT pathway. Prostaglandins Other Lipid Mediat 83(1–2):112–120

    Article  PubMed  CAS  Google Scholar 

  67. Shao J, Evers BM, Sheng H (2004) Prostaglandin E2 synergistically enhances receptor tyrosine kinase-dependent signaling system in colon cancer cells. J Biol Chem 279(14):14287–14293

    Article  PubMed  CAS  Google Scholar 

  68. Reddy BS, Sugie S (1991) Effect of diets high in omega-3 and omega-6 fatty acids on initiation and postinitiation stages of colon carcinogenesis. Cancer Res 51(2):487–491

    PubMed  CAS  Google Scholar 

  69. Mukutmoni-Norris M, Hubbard NE (2000) and Erickson, K.L. Modulation of murine mammary tumor vasculature by dietary n-3 fatty acids in fish oil. Cancer Lett 150(1):101–109

    Article  PubMed  CAS  Google Scholar 

  70. 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(3):883–891

    PubMed  CAS  Google Scholar 

  71. Kobayashi N, Barnard RJ, Henning SM, Elashoff D, Reddy ST, Cohen P, Leung P et al (2006) Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2. Clin Cancer Res 12(15):4662–4670

    Article  PubMed  CAS  Google Scholar 

  72. Dommels YE, Haring MMG, Keestra NGM, Alink GM, van Bladeren PJ, van Ommen B (2003) The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE(2) synthesis and cytotoxicity in human colorectal carcinoma cell lines. Carcinogenesis 24(3):385–392

    Article  PubMed  CAS  Google Scholar 

  73. Boudreau MD, Sohn KH, Rhee SH, Lee SW, Hunt JD, Hwang DH (2001) Suppression of tumor cell growth both in nude mice and in culture by n-3 polyunsaturated fatty acids: mediation through cyclooxygenase-independent pathways. Cancer Res 61(4):1386–1391

    PubMed  CAS  Google Scholar 

  74. Denkins Y, Kempf D, Ferniz M, Nileshwar S, Marchetti D (2005) Role of omega-3 polyunsaturated fatty acids on cyclooxygenase-2 metabolism in brain-metastatic melanoma. J Lipid Res 46(6):1278–1284

    Article  PubMed  CAS  Google Scholar 

  75. 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(11):1919–1925

    Article  PubMed  CAS  Google Scholar 

  76. Malis CD, Weber PC, Leaf A, Bonventre JV (1990) Incorporation of marine lipids into mitochondrial membranes increases susceptibility to damage by calcium and reactive oxygen species: evidence for enhanced activation of phospholipase A2 in mitochondria enriched with n-3 fatty acids. Proc Natl Acad Sci USA 87(22):8845–8849

    Article  PubMed  CAS  Google Scholar 

  77. 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(12):3233–3238

    PubMed  CAS  Google Scholar 

  78. Tsuzuki T, Igarashi M, Miyazawa T (2004) Conjugated eicosapentaenoic acid (EPA) inhibits transplanted tumor growth via membrane lipid peroxidation in nude mice. J Nutr 134(5):1162–1166

    PubMed  CAS  Google Scholar 

  79. Kolar SSN, Barhoumi R, Lupton JR, Chapkin RS (2007) Docosahexaenoic acid and butyrate synergistically induce colonocyte apoptosis by enhancing mitochondrial Ca2+ accumulation. Cancer Res 67(11):5561–5568

    Article  PubMed  CAS  Google Scholar 

  80. Michalak E, Villunger A, Erlacher M, Strasser A (2005) Death squads enlisted by the tumour suppressor p53. Biochem Biophys Res Commun 331(3):786–798

    Article  PubMed  CAS  Google Scholar 

  81. Tsuzuki T, Kambe T, Shibata A, Kawakami Y, Nakagawa K, Miyazawa T (2007) Conjugated EPA activates mutant p53 via lipid peroxidation and induces p53-dependent apoptosis in DLD-1 colorectal adenocarcinoma human cells. Biochim Biophys Acta 1771(1):20–30

    Article  PubMed  CAS  Google Scholar 

  82. Narayanan NK, Narayanan BA, Bosland M, Condin M, Nargi D (2006) Docosahexaenoic acid in combination with celecoxib modulates HSP70 and p53 proteins in prostate cancer cells. Int J Cancer 119(7):1586–1598

    Article  PubMed  CAS  Google Scholar 

  83. Kolar S, 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(5):G935–G943

    Article  PubMed  CAS  Google Scholar 

  84. Yonezawa Y, Hada T, Uryu K, Tsuzuki T, Eitsuka T, Miyazawa T, Murakami-Nakai C, Yoshida H, Mizushina Y (2005) Inhibitory effect of conjugated eicosapentaenoic acid on mammalian DNA polymerase and topoisomerase activities and human cancer cell proliferation. Biochem Pharmacol 70(3):453–460

    Article  PubMed  CAS  Google Scholar 

  85. Nicholson KM, Anderson NG (2002) The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 14(5):381–395

    Article  PubMed  CAS  Google Scholar 

  86. Pahl HL (1999) Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18(49):6853–6866

    Article  PubMed  CAS  Google Scholar 

  87. Clark AS, West K, Streicher S, Denis PA (2002) Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther 1(9):707–717

    PubMed  CAS  Google Scholar 

  88. DeGraffenried LA, Friedrichs WE, Fulcher L, Fernandez G, Silva JM, Peralba JM, Hidalgo M (2003) Eicosapentaenoic acid restores tamoxifen sensitivity in breast cancer cells with high Akt activity. Ann Oncol 14(7):1051–1056

    Article  PubMed  CAS  Google Scholar 

  89. Mirnikjoo B, Brown SE, Kim HF, Marangell LB, Sweatt JD, Weeber EJ (2001) Protein kinase inhibition by omega-3 fatty acids. J Biol Chem 276(14):10888–10896

    Article  PubMed  CAS  Google Scholar 

  90. Schley PD, Jijon HB, Robinson LE, Catherine J, Field CJ (2005) Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells. Breast Cancer Res Treat 92(2):187–195

    Article  PubMed  CAS  Google Scholar 

  91. Cusack JC Jr, Liu R, Baldwin AS Jr (2000) Inducible chemoresistance to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothe cin (CPT-11) in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor-kappaB activation. Cancer Res 60(9):2323–2330

    PubMed  CAS  Google Scholar 

  92. Ross JA, Maingay JP, Fearon JC, Sangster K, Powell JJ (2003) Eicosapentaenoic acid perturbs signalling via the NFkappaB transcriptional pathway in pancreatic tumour cells. Int J Oncol 23(6):1733–1738

    PubMed  CAS  Google Scholar 

  93. 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(1):L84–L89

    PubMed  CAS  Google Scholar 

  94. 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 473(7059):759–763

    Article  CAS  Google Scholar 

  95. He TC, Chan TA, Vogelstein B, Kinzler KW (1999) PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell 99(3):335–345

    Article  PubMed  CAS  Google Scholar 

  96. Gupta RA, Tan J, Krause WF, Geraci MW, Wilson TM, Dey SK, DuBois RN (2000) Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer. Proc Natl Acad Sci 97(24):13275–13280

    Article  PubMed  CAS  Google Scholar 

  97. Park BH, Vogelstein B, Kinzler W (2001) Genetic disruption of PPARdelta decreases the tumorigenicity of human colon cancer cells. Proc Natl Acad Sci 98(5):2598–2603

    Article  PubMed  CAS  Google Scholar 

  98. Gupta RA, Wang D, Katkuri S, Wang H, Dey SK, DuBois RN (2004) Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth. Nat Med 10(3):245–247

    Article  PubMed  CAS  Google Scholar 

  99. Stephen RL, Gustafsson MC, Jarvis M, Tatoud R, Marshall BR, Knight D, Ehrenborg E, Harris AL, Wolf CR, Palmer CN (2004) Activation of peroxisome proliferator-activated receptor delta stimulates the proliferation of human breast and prostate cancer cell lines. Cancer Res 64(9):3162–3170

    Article  PubMed  CAS  Google Scholar 

  100. Reed KR, Sansom OJ, Hayes AJ, Gescher AJ, Peters JM, Clarke AR (2006) PPARdelta status and mismatch repair mediated neoplasia in the mouse intestine. BMC Cancer 6:113

    Article  PubMed  CAS  Google Scholar 

  101. Prolla TA, Baker SM, Harris AC, Tsao LJ, Yao X, Brommer CE, Zheng B, Gordon M, Reneker J, Arnheim M, Shibata D, Bradley A, Liskay RM (1998) Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair. Nat Genet 18(3):276–279

    Article  PubMed  CAS  Google Scholar 

  102. Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK, Kane M, Earabino C, Lipford J, Lindblom A (1994) Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368(6468):258–261

    Article  PubMed  CAS  Google Scholar 

  103. Reed KR, Sansom OJ, Hyes AJ, Gescher AJ, Wintin DJ, Peters JM, Clarke AR (2004) PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine. Oncogene 23(55):8992–8996

    Article  PubMed  CAS  Google Scholar 

  104. Mansen A, Guardiola-Diaz H, Rafter J, Branting C, Gustafsson JA (1996) Expression of the peroxisome proliferator-activated receptor (PPAR) in the mouse colonic mucosa. Biochem Biophys Res Commun 222(3):844–851

    Article  PubMed  CAS  Google Scholar 

  105. 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(9):1058–1061

    Article  PubMed  CAS  Google Scholar 

  106. Sarraf P, Mueller E, Jones D, King FJ, DeAngelo DJ, Partridge JB, Holden SA, Chen LB, Singer S, Fletcher C, Spiegelman BM (1998) Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat Med 4(9):1046–1052

    Article  PubMed  CAS  Google Scholar 

  107. Altiok S, Xu M, Spiegelman BM (1997) PPARgamma induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev 11(15):1987–1998

    Article  PubMed  CAS  Google Scholar 

  108. Shao D, Lazar MA (1997) Peroxisome proliferator activated receptor gamma, CCAAT/enhancer-binding protein alpha, and cell cycle status regulate the commitment to adipocyte differentiation.J Biol Chem 272(34):21473–21478

    Article  PubMed  CAS  Google Scholar 

  109. Morrison RF, Farmer SR (1999) Role of PPARgamma in regulating a cascade expression of cyclin-dependent kinase inhibitors, p18(INK4c) and p21(Waf1/Cip1), during adipogenesis. J Biol Chem 274(24):17088–17097

    Article  PubMed  CAS  Google Scholar 

  110. Han S, Sidell N, Fisher PB, Roman J (2004) Up-regulation of p21 gene expression by peroxisome proliferator-activated receptor gamma in human lung carcinoma cells. Clin Cancer Res 10(6):1911–1919

    Article  PubMed  CAS  Google Scholar 

  111. Debril MB, Renaud JP, Fajas L, Auwerx J (2001) The pleiotropic functions of peroxisome proliferator-activated receptor gamma. J Mol Med 79(1):30–47

    Article  PubMed  CAS  Google Scholar 

  112. Kroll TG, Sarraf P, Pecciarini L, Chen CJ, Mueller E, Spiegelman BM, Fletcher JA (2000) PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]. Science 289(5483): 1357–1360

    Article  PubMed  CAS  Google Scholar 

  113. Ikezoe T, Miller CW, Kawano S, Heaney A, Williamson EA, Hisitake J, Green E, Hofmann W, Taguchi H, Koeffler HP (2001) Mutational analysis of the peroxisome proliferator-activated receptor gamma gene in human malignancies. Cancer Res 61(13):5307–5310

    PubMed  CAS  Google Scholar 

  114. Margeli A, Kouraklis G, Theocharis S (2003) Peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligands and angiogenesis. Angiogenesis 6(3):165–169

    Article  PubMed  CAS  Google Scholar 

  115. Panigrahy D, Singer S, Shen LQ, Butterfield CE, Chen EJ, Moses MA, Kilroy S, Duensing S, Fletcher C, Fletcher JA, Hlatky L, Hahnfeldt P, Folkman J, Kaipainen A (2002) PPARgamma ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. J Clin Invest 110(7):923–932

    PubMed  CAS  Google Scholar 

  116. Guan YF, Zhang YH, Breyer RM, Davis L, Breyer MD (1999) Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human transitional bladder cancer and its role in inducing cell death. Neoplasia 1(4):330–339

    Article  PubMed  CAS  Google Scholar 

  117. Fauconnet S, Lascombe I, Chabannes E, Adessi GL, Desvergene B, Wahli W, Bittard H (2002) Differential regulation of vascular endothelial growth factor expression by peroxisome proliferator-activated receptors in bladder cancer cells. J Biol Chem 277(26):23534–23543

    Article  PubMed  CAS  Google Scholar 

  118. Xin X, Yang S, Kowalski J, Gerritsen ME (1999) Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem 274(13):9116–9121

    Article  PubMed  CAS  Google Scholar 

  119. Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, Madge LA, Schechner JS, Schwabb MB, Polverini PJ, Flores-Riveros JR (1998) Biological action of leptin as an angiogenic factor. Science 281(5383):1683–1686

    Article  PubMed  CAS  Google Scholar 

  120. Goetze S, Bungenstock A, Czupalla C, Eilers F, Stawowy P, Kintscher U, Spencer-Hänsch C, Graf K, Nürnberg B, Law RE, Fleck E, Gräfe M (2002) Leptin induces endothelial cell migration through Akt, which is inhibited by PPARgamma-ligands. Hypertension 40(5):748–754

    Article  PubMed  CAS  Google Scholar 

  121. Freed MI, Allen A, Jorkasky DK, DiCicco RA (1999) Systemic exposure to rosiglitazone is unaltered by food. Eur J Clin Pharmacol 55(1):53–56

    Article  PubMed  CAS  Google Scholar 

  122. Abedin M, Lim J, Tang TB, Park D, Demer LL, Tintut Y (2006) N-3 fatty acids inhibit vascular calcification via the p38-mitogen-activated protein kinase and peroxisome proliferator-activated receptor-gamma pathways. Circ Res 98(6):727–729

    Article  PubMed  CAS  Google Scholar 

  123. Chinetti G, Fruchart JC, Sstaels B (2000) Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res 49(10):497–505

    Article  PubMed  CAS  Google Scholar 

  124. Sethi S, Eastman AY, Eaton JW (1996) Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. J Lab Clin Med 128(1):27–38

    Article  PubMed  CAS  Google Scholar 

  125. Pardini RS (2006) Nutritional intervention with omega-3 fatty acids enhances tumor response to anti-neoplastic agents. Chem Biol Interact 162(2):89–105

    Article  PubMed  CAS  Google Scholar 

  126. Vartak S, Robbins ME, Spector AA (1997) Polyunsaturated fatty acids increase the sensitivity of 36B10 rat astrocytoma cells to radiation-induced cell kill. Lipids 32(3):283–292

    Article  PubMed  CAS  Google Scholar 

  127. Colas S, Paon L, Denis F, Prat M, Louissot P, Hoinard C, LeFloch O, Ogilvie G, Bougnoux P (2004) Enhanced radiosensitivity of rat autochthonous mammary tumors by dietary docosahexaenoic acid. Int J Cancer 109(3):449–454

    Article  PubMed  CAS  Google Scholar 

  128. Benais-Pont G, Dupertuis YM, Kossovsky MP, Nouet P, Allal AS, Buchegger F, Pichard C (2006) Omega-3 polyunsaturated fatty acids and ionizing radiation: combined cytotoxicity on human colorectal adenocarcinoma cells. Nutrition 22(9):931–939

    Article  PubMed  CAS  Google Scholar 

  129. Hardman WE, Sun L, Short N, Cameron LL (2005) Dietary omega-3 fatty acids and ionizing irradiation on human breast cancer xenograft growth and angiogenesis. Cancer Cell Int 5(1):12

    Article  PubMed  CAS  Google Scholar 

  130. Plumb JA, Luo W, Kerr DJ (1993) Effect of polyunsaturated fatty acids on the drug sensitivity of human tumour cell lines resistant to either cisplatin or doxorubicin. Br J Cancer 67(4):728–733

    Article  PubMed  CAS  Google Scholar 

  131. Martin D, Meckling-Gill KA (1996) Omega-3 polyunsaturated fatty acids increase purine but not pyrimidine transport in L1210 leukaemia cells. Biochem J 315(Pt 1):329–333

    PubMed  CAS  Google Scholar 

  132. Swamy MV, Cooma I, Patlolla JMR, 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(2):215–221

    PubMed  CAS  Google Scholar 

  133. Cha MC, Lin A, Meckling KA (2005) Low dose docosahexaenoic acid protects normal colonic epithelial cells from araC toxicity. BMC Pharmacol 5:7

    Article  PubMed  CAS  Google Scholar 

  134. Jordan A, Stein J (2003) Effect of an omega-3 fatty acid containing lipid emulsion alone and in combination with 5-fluorouracil (5-FU) on growth of the colon cancer cell line Caco-2. Eur J Nutr 42(6):324–331

    Article  PubMed  CAS  Google Scholar 

  135. Nakagawa H, Yamamoto D, Kiyozuka Y, Tsuta K, Uemura Y, Hioki K, Tsutsui Y, Tsubura A (2000) Effects of genistein and synergistic action in combination with eicosapentaenoic acid on the growth of breast cancer cell lines. J Cancer Res Clin Oncol 126(8):448–454

    Article  PubMed  CAS  Google Scholar 

  136. Burns CP, North JA (1986) Adriamycin transport and sensitivity in fatty acid-modified leukemia cells. Biochim Biophys Acta 888(1):10–17

    Article  PubMed  CAS  Google Scholar 

  137. Rudra PK, Krokan HE (2001) Cell-specific enhancement of doxorubicin toxicity in human tumour cells by docosahexaenoic acid. Anticancer Res 21(1A):29–38

    PubMed  CAS  Google Scholar 

  138. Ikushima S, Fujiwara F, Todo S, Imashuku S (1991) Effects of polyunsaturated fatty acids on vincristine-resistance in human neuroblastoma cells.Ikushima S, Fujiwara F, Todo S, Imashuku S. Anticancer Res 11(3):1215–1220

    PubMed  CAS  Google Scholar 

  139. Kinsella JE, Black JM (1993) Effects of polyunsaturated fatty acids on the efficacy of antineoplastic agents toward L5178Y lymphoma cells. Biochem Pharmacol 45(9):1881–1887

    Article  PubMed  CAS  Google Scholar 

  140. Norat T, Bingham S, Ferrari P, Slimani N, Jenab M, Mazuir M et al (2005) Meat, fish, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition. J Natl Cancer Inst 97(12):906–916

    Article  PubMed  Google Scholar 

  141. Geelen A, Schouten JM, Kamphuis C, Stam BE, Burema J, Renkema JMS, Bakkers EJ (2007) van’t Veer, P. Kampman, E. Fish consumption, n-3 fatty acids, and colorectal cancer: a meta-analysis of prospective cohort studies. Am J Epidemiol 166(10):1116–1125

    Article  PubMed  Google Scholar 

  142. Thiebaut AC, Kipnis V, Chang SC, Subar AF, Thompson FE, Rosenberg PS et al (2007) Dietary fat and postmenopausal invasive breast cancer in the National Institutes of Health-AARP Diet and Health Study cohort. J Natl Cancer Inst 99(6):451–462

    Article  PubMed  Google Scholar 

  143. Howe LR (2007) Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer. Breast Cancer Res 9(4):210

    Article  PubMed  CAS  Google Scholar 

  144. Dewey A, Baughan C, Dean T, Higgins B, Johnson I (2007) Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of cancer cachexia. Cochrane Database Syst Rev 24(1):CD004597

    Google Scholar 

  145. Moldawer LL, Copeland EM III (1997) Proinflammatory cytokines, nutritional support, and the cachexia syndrome: interactions and therapeutic options. Cancer 79(9):1828–1839

    Article  PubMed  CAS  Google Scholar 

  146. Tisdale MJ (1996) Inhibition of lipolysis and muscle protein degradation by EPA in cancer cachexia. Nutrition 12(Suppl 1):S31–S33

    PubMed  CAS  Google Scholar 

  147. Ross JA, Moses AG, Fearon KC (1999) The anti-catabolic effects of n-3 fatty acids. Curr Opin Clin Nutr Metab Care 2(3):219–226

    Article  PubMed  CAS  Google Scholar 

  148. Wallace FA, Neely SJ, Miles EA, Calder PC (2000) Dietary fats affect macrophage-mediated cytotoxicity towards tumour cells. Immunol Cell Biol 78(1):40–48

    Article  PubMed  CAS  Google Scholar 

  149. Gogos CA, Ginopoulos P, Salsa B, Apostolidou E, Zoumbos NC, Kalfarentzos F (1998) Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial. Cancer 82(2):395–402

    Article  PubMed  CAS  Google Scholar 

  150. Fearon KC, von Meyendfeldt MF, Moses AGW, van Geenen R, Roy A, Gouma DJ, Giacosa A, Van Gossum A, Bauer J, Barber MD, Aaronson NK, Voss AC, Tisdale MJ (2003) 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 52(10):1479–1486

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Universitätsklinikum Carl Gustav Carus, an der Technischen Universität Dresden, Anstalt des öffentlichen Rechts des Freistaates Sachsen, Fetscherstraße 74, Dresden, 01307, Germany

    Axel R. Heller MD, MBA-HCM, DEAA (Senior Executive Physician Klinik und Poliklinik für Anaesthesiologie und Intensivtherapie)

  2. Prinzregent Luitpold Hospital, Scheidegg, Germany

    Martina Wendel

Authors
  1. Axel R. Heller MD, MBA-HCM, DEAA
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martina Wendel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Axel R. Heller MD, MBA-HCM, DEAA .

Editor information

Editors and Affiliations

  1. Health Sciences Center, Department of Health Promotion Sciences, University of Arizona, 1295 N. Martin Ave. 1295, Tucson, 85724-5155, USA

    Ronald Ross Watson

  2. Mel & Enid Zuckerman College of, Public Health, University of Arizona, Tucson, 85724-5163, USA

    Sherma Zibadi

  3. Dept. Nutrition & Dietetics, King's College, Stamford St. 150, London, SE1 9NH, United Kingdom

    Victor R. Preedy

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Heller, A.R., Wendel, M. (2010). Immunomodulation by Fish Oil Derived Polyunsaturated Fatty Acids in Cancer. In: Watson, R., Zibadi, S., Preedy, V. (eds) Dietary Components and Immune Function. Nutrition and Health. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-061-8_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-061-8_10

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-060-1

  • Online ISBN: 978-1-60761-061-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation