Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012, 156(3):186-199 | DOI: 10.5507/bp.2012.093

Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review

Belma Skendera,b, Alena Hyrslova Vaculovaa, Jirina Hofmanovaa,b
a Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i. Brno, Czech Republic
b Department of Physiology and Immunology, Institute of Experimental Biology, Faculty of Sciences, Masaryk Univesity, Brno

Background: Experimental, epidemiological and clinical data substantiate the beneficial role of n-3 polyunsaturated fatty acids (PUFAs) in preventing inflammation and cancer of the colon. This review covers the unsaturated docosahexaenoic fatty acid (DHA), describes some of its important cellular and molecular mechanisms, its interaction with another dietary lipid, butyrate and with endogenous apoptotic regulators of the tumour necrosis factor (TNF) family. We also discuss the clinical impact of this knowledge and the use of these lipids in colon cancer prevention and treatment.

Results: From the literature, DHA has been shown to suppress the growth, induce apoptosis in colon cancer cells in vitro and decrease the incidence and growth of experimental tumours in vivo. Based on these data and our own experimental results, we describe and discuss the possible mechanisms of DHA anticancer effects at various levels of cell organization. We show that DHA can sensitize colon cancer cells to other chemotherapeutic/chemopreventive agents and affect the action of physiological apoptotic regulators of the TNF family.

Conclusion: Use of n-3 PUFAs could be a relatively non-toxic form of supportive therapy for improving colon cancer treatment and slowing down or preventing its recurrence. However, it is necessary to use them with caution, based on solid scientific evidence of their mechanisms of action from the molecular to the cellular and organism levels.

Keywords: polyunsaturated fatty acids, docosahexaenoic acid, colon cancer, apoptosis, cell signalling, anticancer therapy

Received: August 16, 2012; Accepted: September 24, 2012; Prepublished online: October 4, 2012; Published: September 1, 2012  Show citation

ACS AIP APA ASA Harvard Chicago IEEE ISO690 MLA NLM Turabian Vancouver
Skender, B., Hyrslova Vaculova, A., & Hofmanova, J. (2012). Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review. Biomedical papers, 156(3), 186-199. doi: 10.5507/bp.2012.093
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Lunn J, Theobald HE. The Health Effects of Dietary Unsaturated Fatty Acids. Nutrition Bulletin 2006;31:178-224. Go to original source...
    2. Gleissman H, Johnsen JI, Kogner P. Omega-3 fatty acids in cancer, the protectors of good and the killers of evil? Exp Cell Res 2010;316:1365-73. Go to original source... Go to PubMed...
    3. Tvrzicka E, Kremmyda LS, Stankova B, Zak A. Fatty acids as biocompounds: their role in human metabolism, health and disease--a review. Part 1: classification, dietary sources and biological functions. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2011;155:117-130. Go to original source... Go to PubMed...
    4. Kang JX. From fat to fat-1: a tale of omega-3 fatty acids. J Membr Biol 2005;206:165-172. Go to original source... Go to PubMed...
    5. Gomez Candela C, Bermejo Lopez LM, Loria Kohen V. Importance of a balanced omega 6/omega 3 ratio for the maintenance of health. Nutritional recommendations. Nutricion Hospitalaria 2011;26:323-9. Go to PubMed...
    6. Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 2002;56:365-79. Go to original source... Go to PubMed...
    7. Diggle CP. In vitro studies on the relationship between polyunsaturated fatty acids and cancer: tumour or tissue specific effects? Prog Lipid Res 2002;41:240-53. Go to original source... Go to PubMed...
    8. Moyad MA. An introduction to dietary/supplemental omega-3 fatty acids for general health and prevention: part II. Urol Oncol 2005;23:36-48. Go to original source... Go to PubMed...
    9. Rose DP, Connolly JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther 1999;83:217-44. Go to original source... Go to PubMed...
    10. Chapkin RS, Seo J, McMurray DN, Lupton JR. Mechanisms by which docosahexaenoic acid and related fatty acids reduce colon cancer risk and inflammatory disorders of the intestine. Chem Phys Lipids 2008;153:14-23. Go to original source... Go to PubMed...
    11. Wanten GJ, Calder PC. Immune modulation by parenteral lipid emulsions. Am J Clin Nutr 2007;85:1171-84. Go to original source... Go to PubMed...
    12. Berquin IM, Edwards IJ, Chen YQ. Multi-targeted therapy of cancer by omega-3 fatty acids. Cancer Lett 2008;269:363-77. Go to original source... Go to PubMed...
    13. Pardini RS. Nutritional intervention with omega-3 fatty acids enhances tumour response to anti-neoplastic agents. Chem Biol Interact 2006;162:89-105. Go to original source... Go to PubMed...
    14. Scott BL, Bazan NG. Membrane docosahexaenoate is supplied to the developing brain and retina by the liver. Proc Natl Acad Sci U S A 1989;86:2903-7. Go to original source... Go to PubMed...
    15. Kroes R, Schaefer EJ, Squire RA, Williams GM. A review of the safety of DHA45-oil. Food Chem Toxicol 2003;41:1433-46. Go to original source... Go to PubMed...
    16. Rapoport SI, Igarashi M. Can the rat liver maintain normal brain DHA metabolism in the absence of dietary DHA? Prostaglandins Leukot Essent Fatty Acids 2009;81:119-23. Go to original source... Go to PubMed...
    17. Astarita G, Jung KM, Berchtold NC, Nguyen VQ, Gillen DL, Head E, Cotman CW, Piomelli D. Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer's disease. PLoS One 2010;5(9):e12538. Go to original source... Go to PubMed...
    18. Lemaitre-Delaunay D, Pachiaudi C, Laville M, Pousin J, Armstrong M, Lagarde M. Blood compartmental metabolism of docosahexaenoic acid (DHA) in humans after ingestion of a single dose of [(13)C]DHA in phosphatidylcholine. J Lipid Res 1999;40:1867-74. Go to original source...
    19. Garaiova I, Guschina IA, Plummer SF, Tang J, Wang D, Plummer NT. A randomised cross-over trial in healthy adults indicating improved absorption of omega-3 fatty acids by pre-emulsification. Nutr J 2007;6:4. Go to original source... Go to PubMed...
    20. Polozova A, Gionfriddo E, Salem N Jr. Effect of docosahexaenoic acid on tissue targeting and metabolism of plasma lipoproteins. Prostaglandins Leukot Essent Fatty Acids 2006;75:183-90. Go to original source... Go to PubMed...
    21. Ghafoorunissa Vani A, Laxmi R, Sesikeran B. Effects of dietary alpha-linolenic acid from blended oils on biochemical indices of coronary heart disease in Indians. Lipids 2002; 37:1077-86. Go to original source... Go to PubMed...
    22. Watkins SM, Carter LC, German JB. Docosahexaenoic acid accumulates in cardiolipin and enhances HT-29 cell oxidant production. J Lipid Res 1998;39:1583-8. Go to original source...
    23. Moreira LS, Piva B, Gentile LB, Mesquita-Santos FP, D'Avila H, Maya-Monteiro CM, Bozza PT, Bandeira-Melo C, Diaz BL. Cytosolic phospholipase A2-driven PGE2 synthesis within unsaturated fatty acids-induced lipid bodies of epithelial cells. Biochim Biophys Acta 2009;1791:156-65. Go to original source... Go to PubMed...
    24. Wassall SR, Stillwell W. Docosahexaenoic acid domains: the ultimate non-raft membrane domain. Chem Phys Lipids 2008;153:57-63. Go to original source... Go to PubMed...
    25. Simopoulos AP. Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr 1991;54:438-63. Go to original source... Go to PubMed...
    26. Mozaffarian D, Ascherio A, Hu FB, Stampfer MJ, Willett WC, Siscovick DS, Rimm EB. Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men. Circulation 2005;111:157-64. Go to original source... Go to PubMed...
    27. Yeh CS, Wang JY, Cheng TL, Juan CH, Wu CH, Lin SR. Fatty acid metabolism pathway play an important role in carcinogenesis of human colorectal cancers by Microarray-Bioinformatics analysis. Cancer Lett 2006;233:297-308. Go to original source... Go to PubMed...
    28. Horrocks LA, Yeo YK. Docosahexaenoic acid-enriched foods: production and effects on blood lipids. Lipids 1999;34 Suppl:S313. Go to original source... Go to PubMed...
    29. Su HM. Mechanisms of n-3 fatty acid-mediated development and maintenance of learning memory performance. J Nutr Biochem 2010;21:364-73. Go to original source... Go to PubMed...
    30. Young G, Conquer J. Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev 2005;45:1-28. Go to original source... Go to PubMed...
    31. Lukiw WJ, Bazan NG. Inflammatory, apoptotic, and survival gene signaling in Alzheimer's disease. A review on the bioactivity of neuroprotectin D1 and apoptosis. Mol Neurobiol 2010;42:10-16. Go to original source... Go to PubMed...
    32. Habermann N, Lund EK, Pool-Zobel BL, Glei M. Modulation of gene expression in eicosapentaenoic acid and docosahexaenoic acid treated human colon adenoma cells. Genes Nutr 2009;4:73-6. Go to original source... Go to PubMed...
    33. Reddy BS. Types and amount of dietary fat and colon cancer risk: Prevention by omega-3 fatty acid-rich diets. Environ Health Prev Med 2002;7:95-102. Go to original source... Go to PubMed...
    34. Simopoulos AP, Leaf A, Norman Salem. Adequate Intakes / Recommendation Table. [Report on the Internet]. 1999. [cited 12.4.2012]. Available from: http://www.issfal.org/statements/adequate-intakes-recommendation-table.
    35. Institute of Medicine. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. National Academies Press, Washington D.C. [Pre-publication report]. 2002, p.1.1357. [cited 13.4.2012]. Availablefrom:http://www.nal.usda.gov/fnic/DRI/DRI_Energy/energy_full_report.pdf.
    36. BNF (British Nutrition Foundation). n-3 Fatty Acids and Health. [Report on the Internet]. 1999. [cited 15.4.2012]. Avaiable from: http://www.nutrition.org.uk/.
    37. Health Council of the Netherlands. The Hague. Guidelines for a healthy diet 2006. [Report on the Internet]. 2006. [cited 3.4.2012]. Available from: http://www.gezondheidsraad.nl/ sites/default/files/200621E_0.pdf.
    38. WHO in From the Joint FAO/WHO Expert Consultation on Fats and Fatty Acids in Human Nutrition, 10-14 November, 2008, WHO, Geneva. [Report on the Internet]. 2008. [cited 15.4.2012]. Avaiable from: http://foris.fao.org/preview/25553-0ece4cb94ac52f9a25af77ca5cfba7a8c.pdf.
    39. Dostalova J, Dlouhy P, Tlaskal P. Vyzivova doporuceni pro obyvatelstvo Ceske republiky. [Report from the Internet]. 2012. [cited 26.6.2012]. Available from: http://www.vyzivaspol.cz/rubrika-dokumenty/konecne-zneni-vyzivovych doporuceni.html.
    40. Kim W, McMurray DN, Chapkin RS. Chemotherapeutic Properties of n-3 Polyunsaturated Fatty Acids - Old Concepts and New Insights. Immunol Endocr Metab Agents Med Chem 2009;9:38-44. Go to original source... Go to PubMed...
    41. Pauwels EK, Kairemo K. Fatty acid facts, part II: role in the prevention of carcinogenesis, or, more fish on the dish? Drug News Perspect 2008; 21: 504-510. Go to original source... Go to PubMed...
    42. Caygill CP, Charlett A, Hill MJ. Fat, fish, fish oil and cancer. Br J Cancer 1996;74:159-64. Go to original source... Go to PubMed...
    43. Miller BA, Chu KC, Hankey BF, Ries LA. Cancer incidence and mortality patterns among specific Asian and Pacific Islander populations in the U.S. Cancer Causes Control 2008;19:227-56. Go to original source... Go to PubMed...
    44. Micha B. Colorectal Cancer, in Cancer Incidence in Four Member Countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) Compared with US SEER (ed. E.B.K. Freedman L.S., Ries L.A.G., Young J.L.). National Cancer Institute 2006;41-45.
    45. MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, Lim YW, Traina SB, Hilton L, Garland R, Morton SC. Effects of omega-3 fatty acids on cancer risk: a systematic review. JAMA 2006;295:403-15. Go to original source... Go to PubMed...
    46. Ahmed FE. Colon cancer: prevalence, screening, gene expression and mutation, and risk factors and assessment. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2003; 21:65-131. Go to original source... Go to PubMed...
    47. Yang K, Yang W, Mariadason J, Velcich A, Lipkin M, Augenlicht L. Dietary components modify gene expression: implications for carcinogenesis. J Nutr 2005;135:2710-14. Go to original source... Go to PubMed...
    48. Jakobsen CH, Størvold GL, Bremseth H, Follestad T, Sand K, Mack M, Olsen KS, Lundemo AG, Iversen JG, Krokan HE, Schønberg SA. DHA induces ER stress and growth arrest in human colon cancer cells: associations with cholesterol and calcium homeostasis. J Lipid Res 2008;49:2089-100. Go to original source... Go to PubMed...
    49. Ichihara H, Zako K, Komizu Y, Goto K, Ueoka R. Therapeutic effects of hybrid liposomes composed of phosphatidylcholine and docosahexaenoic acid on the hepatic metastasis of colon carcinoma along with apoptosis in vivo. Biol Pharm Bull 2011;34:901-5. Go to original source... Go to PubMed...
    50. Toit-Kohn JL, Louw L, Engelbrecht AM. Docosahexaenoic acid induces apoptosis in colorectal carcinoma cells by modulating the PI3 kinase and p38 MAPK pathways. J Nutr Biochem 2009;20:106-14. Go to original source... Go to PubMed...
    51. 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. Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytes. Carcinogenesis 2002;23:1919-25. Go to original source... Go to PubMed...
    52. Kato T, Hancock RL, Mohammadpour H, McGregor B, Manalo P, Khaiboullina S, Hall MR, Pardini L, Pardini RS. Influence of omega-3 fatty acids on the growth of human colon carcinoma in nude mice. Cancer Lett 2002;187:169-77. Go to original source... Go to PubMed...
    53. Jia Q, Lupton JR, Smith R, Weeks BR, Callaway E, Davidson LA, Kim W, Fan YY, Yang P, Newman RA, Kang JX, McMurray DN, Chapkin RS. Reduced colitis-associated colon cancer in Fat-1 (n-3 fatty acid desaturase) transgenic mice. Cancer Res 2008;68:3985-91. Go to original source... Go to PubMed...
    54. Calviello G, Serini S. Dietary Omega-3 Polyunsaturated Fatty Acids and Cancer. Diet and Cancer 1. Springer; 2010. Albini A, series editor. Go to original source...
    55. Los DA, Murata N. Membrane fluidity and its roles in the perception of environmental signals. Biochim Biophys Acta 2004;1666:142-57. Go to original source... Go to PubMed...
    56. Stillwell W, Shaikh SR, Zerouga M, Siddiqui R, Wassall SR. Docosahexaenoic acid affects cell signaling by altering lipid rafts. Reprod Nutr Dev 2005;45:559-79. Go to original source... Go to PubMed...
    57. Pohl J, Ring A, Ehehalt R, Herrmann T, Stremmel W. New concepts of cellular fatty acid uptake: role of fatty acid transport proteins and of caveolae. Proc Nutr Soc 2004;63,259-62. Go to original source... Go to PubMed...
    58. Bougnoux P, Hajjaji N, Ferrasson MN, Giraudeau B, Couet C, Le Floch O. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial. Br J Cancer 2009;101:1978-85. Go to original source... Go to PubMed...
    59. Rogers KR, Kikawa KD, Mouradian M, Hernandez K, McKinnon KM, Ahwah SM, Pardini RS. Docosahexaenoic acid alters epidermal growth factor receptor-related signaling by disrupting its lipid raft association. Carcinogenesis 2010;31:1523-30. Go to original source... Go to PubMed...
    60. Seo J, Barhoumi R, Johnson AE, Lupton JR, Chapkin RS. Docosahexaenoic acid selectively inhibits plasma membrane targeting of lipidated proteins. FASEB J 2006;20,770-2. Go to original source... Go to PubMed...
    61. Chapkin RS, Wang N, Fan YY, Lupton JR, Prior IA. Docosahexaenoic acid alters the size and distribution of cell surface microdomains. Biochim Biophys Acta 2008;1778:466-71. Go to original source... Go to PubMed...
    62. Sampath H, Ntambi JM. Polyunsaturated fatty acid regulation of genes of lipid metabolism. Annu Rev Nutr 2005;25:317-40. Go to original source... Go to PubMed...
    63. Calviello G, Serini S, Piccioni E. n-3 polyunsaturated fatty acids and the prevention of colorectal cancer: molecular mechanisms involved. Curr Med Chem 2007;14:3059-69. Go to original source... Go to PubMed...
    64. Cha MC, Lin A, Meckling KA. Low dose docosahexaenoic acid protects normal colonic epithelial cells from araC toxicity. BMC Pharmacol 2005;5:7. Go to original source... Go to PubMed...
    65. Murray NR, Weems C, Chen L, Leon J, Yu W, Davidson LA, Jamieson L, Chapkin RS. Thompson, E. A. Fields, A. P. Protein kinase C betaII and TGFbetaRII in omega-3 fatty acid-mediated inhibition of colon carcinogenesis. J Cell Biol 2002;157:915-20. Go to original source... Go to PubMed...
    66. Engelbrecht AM, Toit-Kohn JL, Ellis B, Thomas M, Nell T, Smith R. Differential induction of apoptosis and inhibition of the PI3-kinase pathway by saturated, monounsaturated and polyunsaturated fatty acids in a colon cancer cell model. Apoptosis 2008;13:1368-77. Go to original source... Go to PubMed...
    67. Dimitriadis A, Vincan E, Mohammed IM, Roczo N, Phillips WA, Baindur-Hudson S. Expression of Wnt genes in human colon cancers. Cancer Lett 2001;166:185-91. Go to original source... Go to PubMed...
    68. Narayanan BA, Narayanan NK, Desai D, Pittman B, Reddy BS. Effects of a combination of docosahexaenoic acid and 1,4-phenylene bis(methylene) selenocyanate on cyclooxygenase 2, inducible nitric oxide synthase and beta-catenin pathways in colon cancer cells. Carcinogenesis 2004;25:2443-9. Go to original source... Go to PubMed...
    69. Fujise T, Wakiri R, Kakimoto T, Shiraishi R, Sakata Y, Wu B, Tsunada S, Ootani A, Fujimoto K. Long-term feeding of various fat diets modulates azoxymethane-induced colon carcinogenesis through Wnt/beta-catenin signaling in rats. Am J Physiol Gastrointest Liver Physiol 2007;292:G1150-6. Go to original source... Go to PubMed...
    70. Habermann N, Schon A, Lund EK, Glei M. Fish fatty acids alter markers of apoptosis in colorectal adenoma and adenocarcinoma cell lines but fish consumption has no impact on apoptosis-induction ex vivo. Apoptosis 2010;15:621-30. Go to original source... Go to PubMed...
    71. Giros A, Grzybowski M, Sohn VR, Pons E, Fernandez-Morales J, Xicola RM, Sethi P, Grzybowski J. Regulation of colorectal cancer cell apoptosis by the n-3 polyunsaturated fatty acids Docosahexaenoic and Eicosapentaenoic. Cancer Prev Res (Phila) 2009;2:732-42. Go to original source... Go to PubMed...
    72. Di Paola M, Lorusso M. Interaction of free fatty acids with mitochondria: coupling, uncoupling and permeability transition. Biochim Biophys Acta 2006;1757:1330-7. Go to original source... Go to PubMed...
    73. McMillin JB, Dowhan W. Cardiolipin and apoptosis. Biochim Biophys Acta 2002;1585:97-107. Go to original source... Go to PubMed...
    74. Cristea IM, Degli Esposti M. Membrane lipids and cell death: an overview. Chem Phys Lipids 2004;129:133-60. Go to original source... Go to PubMed...
    75. Kagan VE, Bayir HA, Belikova NA, Kapralov O, Tyurina YY, Tyurin VA, Jiang J, Stoyanovsky DA, Wipf P, Kochanek PM, Greenberger JS, Pitt B, Shvedova AA, Borisenko G. Cytochrome c/cardiolipin relations in mitochondria: a kiss of death. Free Radic Biol Med 2009;46:1439-53. Go to original source... Go to PubMed...
    76. Basu A, DuBois G, Haldar S. Posttranslational modifications of Bcl2 family members--a potential therapeutic target for human malignancy. Front Biosci 2006;11:1508-21. Go to original source... Go to PubMed...
    77. Slagsvold JE, Pettersen CH, Størvold GL, Follestad T, Krokan HE, Schønberg SA. DHA alters expression of target proteins of cancer therapy in chemotherapy resistant SW620 colon cancer cells. Nutr Cancer 2010;62:611-21. Go to original source... Go to PubMed...
    78. Hofmanova J, Soucek K, Vaculova A, Kozubik A. Fatty Acids in the Modulation of Reactive Oxygen Species Balance in Cnacer. Speringer, 2008, in Oxidants in Biology, Vol. VIII. (ed. P.A.D. Giuseppe Valacchi). 2008. p.129-153. Go to original source...
    79. Das BR, Nagpal JK. Understanding the biology of oral cancer. Med Sci Monit 2002; 8: RA258-267.
    80. Schonberg SA, Lundemo AG, Fladvad T, Holmgren K, Bremseth H, Nilsen A, Gederaas O, Tvedt KE, Egeberg KW, Krokan HE. Closely related colon cancer cell lines display different sensitivity to polyunsaturated fatty acids, accumulate different lipid classes and downregulate sterol regulatory element-binding protein 1. FEBS J 2006;273:2749-65. Go to original source... Go to PubMed...
    81. Siddiqui RA, Harvey K, Stillwell W. Anticancer properties of oxidation products of docosahexaenoic acid. Chem Phys Lipids 2008;153:47-56. Go to original source... Go to PubMed...
    82. Ding WQ, Vaught JL, Yamauchi H, Lind SE. Differential sensitivity of cancer cells to docosahexaenoic acid-induced cytotoxicity: the potential importance of down-regulation of superoxide dismutase 1 expression. Mol Cancer Ther 2004;3:1109-17. Go to original source... Go to PubMed...
    83. Hofmanova J, Vaculova A, Koubkova Z, Hyzd'alova M, Kozubik A. Human fetal colon cells and colon cancer cells respond differently to butyrate and PUFAs. Mol Nutr Food Res 2009;53 Suppl 1:S102-13. Go to original source... Go to PubMed...
    84. Sato SB, Sato S, Kawamoto J, Kurihara T. Differential roles of internal and terminal double bonds in docosahexaenoic acid: Comparative study of cytotoxicity of polyunsaturated fatty acids to HT-29 human colorectal tumor cell line. Prostaglandins Leukot Essent Fatty Acids 2010;84:31-7. Go to original source... Go to PubMed...
    85. Narayanan BA, Narayanan NK, Simi B, Reddy BS. Modulation of inducible nitric oxide synthase and related proinflammatory genes by the omega-3 fatty acid docosahexaenoic acid in human colon cancer cells. Cancer Res 2003;63:972-9.
    86. Furstenberger G, Krieg P, Muller-Decker K, Habenicht AJ. What are cyclooxygenases and lipoxygenases doing in the driver's seat of carcinogenesis? Int J Cancer 2006;119:2247-54. Go to original source... Go to PubMed...
    87. 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;79:935-45. Go to original source... Go to PubMed...
    88. Wada M, Delong CJ, Hong YH, Rieke CJ, Song I, Sidhu RS, Yuan C, Warnock M, Schmaier AH, Yokoyama C, Smyth EM, Wilson SJ, Fitzgerald GA, Garavito RM, Sui DX, Regan JW, Smith WL. Enzymes and receptors of prostaglandin pathways with arachidonic acid- vs. eicosapentaenoic acid-derived substrates and products. J Biol Chem 2007;282:22254-66. Go to original source... Go to PubMed...
    89. Serhan CN, Chiang N. Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Br J Pharmacol 2008;153 Suppl 1:S200-15. Go to original source... Go to PubMed...
    90. Swamy MV, Cooma I, Patlolla JM, Simi B, Reddy BS, Rao CV. 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 2004;3:215-21. Go to original source...
    91. Habbel P, Weylandt KH, Lichopoj K, Nowak J, Purschke M, Wang JD, He CW, Baumgart DC, Kang JX. Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells. World J Gastroenterol 2009;15:1079-84. Go to original source... Go to PubMed...
    92. Agarwal B, Swaroop P, Protiva P, Raj SV, Shirin H, Holt PR. Cox-2 is needed but not sufficient for apoptosis induced by Cox-2 selective inhibitors in colon cancer cells. Apoptosis 2003;8:649-54. Go to original source... Go to PubMed...
    93. Boudreau MD, Swaroop P, Protiva P, Raj SV, Shirin H, Holt PR. 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 2001;61:1386-91. Go to PubMed...
    94. Calviello G, Di Nicuolo F, Serini S, Piccioni E, Boninsegna A, Maggiano N, Ranelletti FO, Palozza P. Docosahexaenoic acid enhances the susceptibility of human colorectal cancer cells to 5-fluorouracil. Cancer Chemother Pharmacol 2005;55:12-20. Go to original source... Go to PubMed...
    95. Kikawa KD, Noah T, Ahwah SM, Pardini RS. Docosahexaenoic Acid (DHA) Induces P53-Dependent Growth Inhibition in Transformed Colon and Lung Cell Lines Expressing Wildtype P53. Journal of Cancer Science and Therapy 2011;9:1523-30. Go to original source...
    96. Pegorier JP, Le May C, Girard J. Control of gene expression by fatty acids. J Nutr 2004;134:2444S-2449S. Go to original source... Go to PubMed...
    97. Horia E, Watkins BA. Complementary actions of docosahexaenoic acid and genistein on COX-2, PGE2 and invasiveness in MDA-MB-231 breast cancer cells. Carcinogenesis 2007;28:809-15. Go to original source... Go to PubMed...
    98. Ponferrada A, Caso JR, Alou L, Colon A, Sevillano D, Moro MA, Lizasoain I, Menchen P, Gomez-Lus ML, Lorenzo P, Cos E, Leza JC, Menchen L. The role of PPARgamma on restoration of colonic homeostasis after experimental stress-induced inflammation and dysfunction. Gastroenterology 2007;132:1791-1803. Go to original source... Go to PubMed...
    99. Zand H, Rahimipour A, Salimi S, Shafiee SM. Docosahexaenoic acid sensitizes Ramos cells to Gamma-irradiation-induced apoptosis through involvement of PPAR-gamma activation and NF-kappaB suppression. Mol Cell Biochem 2008;317:113-120. Go to original source... Go to PubMed...
    100. Singer P, Shapiro H, Theilla M, Anbar R, Singer J, Cohen J. Anti-inflammatory properties of omega-3 fatty acids in critical illness: novel mechanisms and an integrative perspective. Intensive Care Med 2008;34:1580-92. Go to original source... Go to PubMed...
    101. Yang WL, Frucht H. Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells. Carcinogenesis 2001;22:1379-83. Go to original source... Go to PubMed...
    102. Hardman WE, Moyer MP, Cameron IL. Consumption of an omega-3 fatty acids product, INCELL AAFA, reduced side-effects of CPT-11 (irinotecan) in mice. Br J Cancer 2002;86:983-8. Go to original source... Go to PubMed...
    103. Gerner EW, Ignatenko NA, Lance P, Hurley LH. A comprehensive strategy to combat colon cancer targeting the adenomatous polyposis coli tumor suppressor gene. Ann N Y Acad Sci 2005;1059:97-105. Go to original source... Go to PubMed...
    104. Paulsen JE, Elvsaas IK, Steffensen IL, Alexander J. A fish oil derived concentrate enriched in eicosapentaenoic and docosahexaenoic acid as ethyl ester suppresses the formation and growth of intestinal polyps in the Min mouse. Carcinogenesis 1997;18: 1905-10. Go to original source... Go to PubMed...
    105. Arango D, Corner GA, Wadler S, Catalano PJ, Augenlicht LH. c-myc/p53 interaction determines sensitivity of human colon carcinoma cells to 5-fluorouracil in vitro and in vivo. Cancer Res 2001;61:4910-5.
    106. Davidson LA, Nguyen DV, Hokanson RM, Callaway ES, Isett RB, Turner ND, Dougherty ER, Wang N, Lupton JR, Carroll RJ, Chapkin RS. Chemopreventive n-3 polyunsaturated fatty acids reprogram genetic signatures during colon cancer initiation and progression in the rat. Cancer Res 2004;64:6797-6804. Go to original source... Go to PubMed...
    107. Narayanan BA, Narayanan NK, Reddy BS. Docosahexaenoic acid regulated genes and transcription factors inducing apoptosis in human colon cancer cells. Int J Oncol 2001;19:1255-62. Go to original source... Go to PubMed...
    108. Calviello G, Resci F, Serini S, Piccioni E, Toesca A, Boninsegna A, Monego G, Ranelletti FO, Palozza P. Docosahexaenoic acid induces proteasome-dependent degradation of beta-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2. Carcinogenesis 2007;28:1202-9. Go to original source... Go to PubMed...
    109. Iigo M, Nakagawa T, Ishikawa C, Iwahori Y, Asamoto M, Yazawa K, Araki E, Tsuda H. Inhibitory effects of docosahexaenoic acid on colon carcinoma 26 metastasis to the lung. Br J Cancer 1997;75:650-5. Go to original source... Go to PubMed...
    110. Suzuki I, Iigo M, Ishikawa C, Kuhara T, Asamoto M, Kunimoto T, Moore MA, Yazawa K. Inhibitory effects of oleic and docosahexaenoic acids on lung metastasis by colon-carcinoma-26 cells are associated with reduced matrix metalloproteinase-2 and -9 activities. Int J Cancer 1997;73:607-12. Go to original source... Go to PubMed...
    111. Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A. The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur J Cancer 2009;45:2077-86. Go to original source... Go to PubMed...
    112. Ibrahim A, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A. Anti-inflammatory and anti-angiogenic effect of long chain n-3 polyunsaturated fatty acids in intestinal microvascular endothelium. Clin Nutr 2011;30:678-87. Go to original source... Go to PubMed...
    113. Conklin KA. Dietary polyunsaturated fatty acids: impact on cancer chemotherapy and radiation. Altern Med Rev 2002;7:4-21.
    114. Kokura S, Nakagawa S, Hara T, Boku Y, Naito Y, Yoshida N, Yoshikawa T. Enhancement of lipid peroxidation and of the antitumor effect of hyperthermia upon combination with oral eicosapentaenoic acid. Cancer Lett 2002;185:139-44. Go to original source... Go to PubMed...
    115. Norman HA, Butrum RR, Feldman E, Heber D, Nixon D, Picciano MF, Rivlin R, Simopoulos A, Wargovich MJ, Weisburger EK, Zeisel SH. The role of dietary supplements during cancer therapy. J Nutr 2003;133:3794S-3799S. Go to original source... Go to PubMed...
    116. Jho DH, Cole SM, Lee EM, Espat NJ. Role of omega-3 fatty acid supplementation in inflammation and malignancy. Integr Cancer Ther 2004;3:98-111. Go to original source... Go to PubMed...
    117. Hajjaji N, Bougnoux P. Selective sensitization of tumors to chemotherapy by marine-derived lipids: A review. Cancer Treat Rev. 2012. [Epub ahead of print] doi: S0305-7372(12)00147-8 [pii]10.1016/j.ctrv.2012.07.001. Go to original source...
    118. Biondo PD, Brindley DN, Sawyer MB, Field CJ. The potential for treatment with dietary long-chain polyunsaturated n-3 fatty acids during chemotherapy. J Nutr Biochem 2008;19:787-96. Go to original source... Go to PubMed...
    119. Fauser JK, Prisciandaro LD, Cummins AG, Howarth GS. Fatty acids as potential adjunctive colorectal chemotherapeutic agents. Cancer Biol Ther 2001;11:724-31. Go to original source...
    120. Cockbain AJ, Toogood GJ, Hull MA. Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer. An International Journal of gastroenterology and Hepatology 2010;61:135-49. Go to original source...
    121. Fracasso PM, Picus J, Wildi JD, Goodner SA, Creekmore AN, Gao F, Govindan R, Ellis MJ, Tan BR, Linette GP, Fu CJ, Pentikis HS, Zumbrun SC, Egorin MJ, Bellet RE. Phase 1 and pharmacokinetic study of weekly docosahexaenoic acid-paclitaxel, Taxoprexin, in resistant solid tumor malignancies. Cancer Chemother Pharmacol 2009;63:451-8. Go to original source... Go to PubMed...
    122. Kuznetsova L, Chen J, Sun L, Wu X, Pepe A, Veith JM, Pera P, Bernacki RJ. Syntheses and evaluation of novel fatty acid-second-generation taxoid conjugates as promising anticancer agents. Bioorg Med Chem Lett 2006;16:974-7. Go to original source... Go to PubMed...
    123. Kello M, Mikes J, Jendzelovsky R, Koval J, Fedorocko P. PUFAs enhance oxidative stress and apoptosis in tumour cells exposed to hypericin-mediated PDT. Photochem Photobiol Sci 2010;9:1244-51. Go to original source... Go to PubMed...
    124. Baumgartner M, Sturlan S, Roth E, Wessner B, Bachleitner-Hofmann T. Enhancement of arsenic trioxide-mediated apoptosis using docosahexaenoic acid in arsenic trioxide-resistant solid tumor cells. Int J Cancer 2004;112:707-12. Go to original source... Go to PubMed...
    125. Timmer-Bosscha H, Mulder NH, de Vries EG. Modulation of cis-diamminedichloroplatinum(II) resistance: a review. Br J Cancer 1992;66:227-38. Go to original source... Go to PubMed...
    126. Yam D, Peled A, Shinitzky M. Suppression of tumor growth and metastasis by dietary fish oil combined with vitamins E and C and cisplatin. Cancer Chemother Pharmacol 2001;47:34-40. Go to original source... Go to PubMed...
    127. Murphy RA, Mourtzakis M,Chu QS, Baracos VE, Reiman T, Mazurak VC.
    128. Jordan A, Stein J. 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 2003;42:324-31. Go to original source... Go to PubMed...
    129. Xue H, Le Roy S, Sawyer MB, Field CJ, Dieleman LA, Baracos VE. Single and combined supplementation of glutamine and n-3 polyunsaturated fatty acids on host tolerance and tumour response to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11)/5-fluorouracil chemotherapy in rats bearing Ward colon tumour. Br J Nutr 2009;102:434-42. Go to original source... Go to PubMed...
    130. Gervaz P, Rubbia-Brandt L, Andres A, Majno P, Roth A, Morel P, Mentha G. Neoadjuvant chemotherapy in patients with stage IV colorectal cancer: a comparison of histological response in liver metastases, primary tumors, and regional lymph nodes. Ann Surg Oncol 2010;17:2714-9. Go to original source... Go to PubMed...
    131. Narayanan NK, Narayanan BA, Bosland M, Condon MS, Nargi D. Docosahexaenoic acid in combination with celecoxib modulates HSP70 and p53 proteins in prostate cancer cells. Int J Cancer 2006;119:1586-98. Go to original source... Go to PubMed...
    132. Reddy BS, Patlolla JM, Simi B, Wang SH, Rao CV. Prevention of colon cancer by low doses of celecoxib, a cyclooxygenase inhibitor, administered in diet rich in omega-3 polyunsaturated fatty acids. Cancer Res 2005;65:8022-7. Go to original source... Go to PubMed...
    133. Haynes NM, van der Most RG, Lake RA, Smyth MJ. Immunogenic anti-cancer chemotherapy as an emerging concept. Curr Opin Immunol 2008;20:545-57. Go to original source... Go to PubMed...
    134. Molinari R, D'Eliseo D, Manzi L, Zolla L, Velotti, F, Merendino N. The n3-polyunsaturated fatty acid docosahexaenoic acid induces immunogenic cell death in human cancer cell lines via pre-apoptotic calreticulin exposure. Cancer Immunol Immunother 2011;60:1503-7. Go to original source... Go to PubMed...
    135. Yaqoob P, Newsholme EA, Calder PC. The effect of dietary lipid manipulation on rat lymphocyte subsets and proliferation. Immunology 1994;82:603-10. Go to PubMed...
    136. Kelley DS, Taylor PC, Nelson GJ, Schmidt PC, Ferretti A, Erickson KL, Yu R, Chandra RK. Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 1999;34:317-24. Go to original source... Go to PubMed...
    137. Ambrozova G, Pekarova M, Lojek A. Effect of polyunsaturated fatty acids on the reactive oxygen and nitrogen species production by raw 264.7 macrophages. Eur J Nutr 2009;49:133-9. Go to original source... Go to PubMed...
    138. Serini S, Fasano E, Piccioni E, Cittadini AR, Calviello G. Dietary n-3 polyunsaturated fatty acids and the paradox of their health benefits and potential harmful effects. Chem Res Toxicol 2011;24:2093-105. Go to original source... Go to PubMed...
    139. Hofmanova J, Vaculova A, Kozubik A. Regulation of the metabolism of polyunsaturated fatty acids and butyrate in colon cancer cells. Curr Pharm Biotechnol. 2011; doi: BSP/CPB/E-Pub/0000102-13-5 [pii]. Go to original source...
    140. Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol 2011;17:1519-28. Go to original source... Go to PubMed...
    141. Scharlau D, Borowicki A, Habermann N, Hofmann T, Klenow S, Miene C, Munjal U, Stein K, Glei M. Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat Res 2009;682:39-53. Go to original source... Go to PubMed...
    142. Chapkin RS, Hong MY, Fan YY, Davidson LA, Sanders LM, Henderson CE, Barhoumi R, Burghardt RC, Turner ND, Lupton JR. Dietary n-3 PUFA alter colonocyte mitochondrial membrane composition and function. Lipids 2002;37:193-9. Go to original source... Go to PubMed...
    143. Kolar SS, Barhoumi R, Callaway ES, Fan YY, Wang N, Lupton JR, Chapkin RS. Synergy between docosahexaenoic acid and butyrate elicits p53-independent apoptosis via mitochondrial Ca(2+) accumulation in colonocytes. Am J Physiol Gastrointest Liver Physiol 2007;293:G935-43. Go to original source... Go to PubMed...
    144. Vanamala J, Glagolenko A, Yang P, Carroll RJ, Murphy ME, Newman RA, Ford JR, Braby LA. Dietary fish oil and pectin enhance colonocyte apoptosis in part through suppression of PPARdelta/PGE2 and elevation of PGE3. Carcinogenesis 2008;29:790-6. Go to original source... Go to PubMed...
    145. Shah MS, Schwartz SL, Zhao C, Davidson LA, Zhou B, Lupton JR, Ivanov I, Chapkin RS. Integrated microRNA and mRNA expression profiling in a rat colon carcinogenesis model: effect of a chemo-protective diet. Physiol Genomics 2011;43:640-54. Go to original source... Go to PubMed...
    146. Hofmanova J, Vaculova A, Kozubik A. Polyunsaturated fatty acids sensitize human colon adenocarcinoma HT-29 cells to death receptor-mediated apoptosis. Cancer Lett 2005;218:33-41. Go to original source... Go to PubMed...
    147. Hofmanova J, Ciganek M, Slavik J, Kozubik A, Stixova L, Vaculova A, Dusek L, Machala M. Lipid alterations in human colon epithelial cells induced to differentiation and/or apoptosis by butyrate and polyunsaturated fatty acids. J Nutr Biochem. 2011. [Eupub ahead of print]. doi: S0955-2863(11)00083-0 [pii]10.1016/j.jnutbio.2011.02.010. Go to original source...
    148. Kielar ML, Jeyarajah DR, Zhou XJ, Lu CY. Docosahexaenoic acid ameliorates murine ischemic acute renal failure and prevents increases in mRNA abundance for both TNF-alpha and inducible nitric oxide synthase. J Am Soc Nephrol 2003;14:389-96. Go to original source... Go to PubMed...
    149. Mathew SJ, Haubert D, Kronke M, Leptin M. Looking beyond death: a morphogenetic role for the TNF signalling pathway. J Cell Sci 2009;122:1939-46. Go to original source... Go to PubMed...
    150. Kishida E, Tajiri M, Masuzawa Y. Docosahexaenoic acid enrichment can reduce L929 cell necrosis induced by tumor necrosis factor. Biochim Biophys Acta 2006;1761:454-62. Go to original source... Go to PubMed...
    151. Vaculova A, Hofmanova J, Andera L, Kozubik A. TRAIL and docosahexaenoic acid cooperate to induce HT-29 colon cancer cell death. Cancer Lett 2005;229:43-8. Go to original source... Go to PubMed...
    152. Andera L. Signaling activated by the death receptors of the TNFR family. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2009;153:173-80. Go to original source... Go to PubMed...
    153. Dupertuis YM, Meguid MM, Pichard C. Colon cancer therapy: new perspectives of nutritional manipulations using polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care 2007;10:427-32. Go to original source... Go to PubMed...
    154. Adolph M, Heller AR, Koch T, Koletzko B, Kreymann KG, Krohn K, Pscheidl E, Senkal M. Lipid emulsions - Guidelines on Parenteral Nutrition, Chapter 6. Ger Med Sci 2009; 7: Doc22. Go to original source...
    155. Grimm H, Mertes N, Goeters C, Schlotzer E, Mayer K, Grimminger F, Furst P. Improved fatty acid and leukotriene pattern with a novel lipid emulsion in surgical patients. Eur J Nutr 2006;45:55-60. Go to original source... Go to PubMed...
    156. Sukhotnik I, Slijper N, Pollak Y, Chemodanov E, Shaoul R, Coran AG, Mogilner JG. Parenteral omega-3 fatty acids (Omegaven) modulate intestinal recovery after intestinal ischemia-reperfusion in a rat model. J Pediatr Surg 2011;46:1353-60. Go to original source... Go to PubMed...
    157. Ryan AS, Keske MA, Hoffman JP, Nelson EB. Clinical overview of algal-docosahexaenoic acid: effects on triglyceride levels and other cardiovascular risk factors. Am J Ther 2009;16:183-92. Go to original source... Go to PubMed...
    158. Finco C, Magnanini P, Sarzo G, Vecchiato M, Luongo B, Savastano S, Bortoliero M, Barison P. Prospective randomized study on perioperative enteral immunonutrition in laparoscopic colorectal surgery. Surg Endosc 2007;21:1175-9. Go to original source... Go to PubMed...
    159. Dupertuis YM, Meguid MM, Pichard C. Advancing from immunonutrition to a pharmaconutrition: a gigantic challenge. Curr Opin Clin Nutr Metab Care 2009;12:398-403. Go to original source... Go to PubMed...
    160. Hofmanova J, Zadak Z, Hyspler R, Mikeska J, Zdansky P, Vaculova A, Netikova J, Kozubik A. The effects of parenteral lipid emulsions on cancer and normal human colon epithelial cells in vitro. Physiol Res 2005;54:409-18. Go to original source...
    161. Paccagnella A, Morassutti I, Rosti G. Nutritional intervention for improving treatment tolerance in cancer patients. Curr Opin Oncol 2011;23:322-30. Go to original source... Go to PubMed...
    162. Senkal M, Haaker R, Linseisen J, Wolfram G, Homann HH, Stehle P. Preoperative oral supplementation with long-chain Omega-3 fatty acids beneficially alters phospholipid fatty acid patterns in liver, gut mucosa, and tumor tissue. JPEN J Parenter Enteral Nutr 2005;29:236-40. Go to original source... Go to PubMed...
    163. Colomer R, Moreno-Nogueira JM, Garcia-Luna PP, Garcia-Peris P, Garcia-de Lorenzo A, Zarazaga A, Quecedo L, del Llano J, Usan L, Casimiro C. N-3 fatty acids, cancer and cachexia: a systematic review of the literature. Br J Nutr 2007;97:823-31. Go to original source... Go to PubMed...
    164. Calder PC n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases.. Am J Clin Nutr 2006;83:1505S-1519S. Go to PubMed...

    Return to the content