Skip to main content

Advertisement

SpringerLink
Log in

Mechanisms by Which Pleiotropic Amphiphilic n−3 PUFA Reduce Colon Cancer Risk

  • Molecular Biology (S Anant, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

Colorectal cancer is one of the major causes of cancer-related mortality in both men and women worldwide. Genetic susceptibility and diet are primary determinants of cancer risk and tumor behavior. Experimental, epidemiological, and clinical data substantiate the beneficial role of n−3 polyunsaturated fatty acids (PUFA) in preventing chronic inflammation and colon cancer. From a mechanistic perspective, n−3 PUFA are pleiotropic and multifaceted with respect to their molecular mechanisms of action. For example, this class of dietary lipid uniquely alters membrane structure/cytoskeletal function, impacting membrane receptor function and downstream signaling cascades, including gene expression profiles and cell phenotype. In addition, n−3 PUFA can synergize with other potential anti-tumor agents, such as fermentable fiber and curcumin. With the rising prevalence of diet-induced obesity, there is also an urgent need to elucidate the link between chronic inflammation in adipose tissue and colon cancer risk in obesity. In this review, we will summarize recent developments linking n−3 PUFA intake, membrane alterations, epigenetic modulation, and effects on obesity-associated colon cancer risk.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    PubMed  Google Scholar 

  2. Siegel R, Naishadham D, Jemal A. Cancer statistics for Hispanics/Latinos, 2012. CA Cancer J Clin. 2012;62(5):283–98.

    PubMed  Google Scholar 

  3. Colditz GA, Sellers TA, Trapido E. Epidemiology—identifying the causes and preventability of cancer? Nat Rev Cancer. 2006;6(1):75–83.

    PubMed  CAS  Google Scholar 

  4. Vargas AJ, Thompson PA. Diet and nutrient factors in colorectal cancer risk. Nutr Clin Pract. 2012;27(5):613–23.

    PubMed  Google Scholar 

  5. Ben Q, Sun Y, Chai R, Qian A, Xu B, Yuan Y. Dietary fiber intake reduces risk for colorectal adenoma: a meta-analysis. Gastroenterology. 2014;146(3):689–99. e6.

    PubMed  CAS  Google Scholar 

  6. Zhang J, Zhang L, Ye X, Chen L, Zhang L, Gao Y, et al. Characteristics of fatty acid distribution is associated with colorectal cancer prognosis. Prostaglandins Leukot Essent Fatty Acids. 2013;88(5):355–60.

    PubMed  CAS  Google Scholar 

  7. Guesnet P, Alessandri JM. Docosahexaenoic acid (DHA) and the developing central nervous system (CNS)—implications for dietary recommendations. Biochimie. 2011;93(1):7–12.

    PubMed  CAS  Google Scholar 

  8. Davidson LA, Wang N, Shah MS, Lupton JR, Ivanov I, Chapkin RS. n-3 Polyunsaturated fatty acids modulate carcinogen-directed non-coding microRNA signatures in rat colon. Carcinogenesis. 2009;30(12):2077–84.

    PubMed  CAS  PubMed Central  Google Scholar 

  9. Hull MA. Omega-3 polyunsaturated fatty acids. Best Pract Res Clin Gastroenterol. 2011;25(4–5):547–54.

    PubMed  CAS  Google Scholar 

  10. Cho Y, Turner ND, Davidson LA, Chapkin RS, Carroll RJ, Lupton JR. A chemoprotective fish oil/pectin diet enhances apoptosis via Bcl-2 promoter methylation in rat azoxymethane-induced carcinomas. Exp Biol Med (Maywood). 2012;237(12):1387–93.

    CAS  Google Scholar 

  11. Jing K, Wu T, Lim K. Omega-3 polyunsaturated fatty acids and cancer. Anticancer Agents Med Chem. 2013;13(8):1162–77.

    PubMed  CAS  Google Scholar 

  12. Horejsi V, Hrdinka M. Membrane microdomains in immunoreceptor signaling. FEBS Lett. 2014

  13. Pike LJ. Lipid rafts: bringing order to chaos. J Lipid Res. 2003;44(4):655–67.

    PubMed  CAS  Google Scholar 

  14. Head BP, Patel HH, Insel PA. Interaction of membrane/lipid rafts with the cytoskeleton: impact on signaling and function: membrane/lipid rafts, mediators of cytoskeletal arrangement and cell signaling. Biochim Biophys Acta. 2014;1838(2):532–45. The dynamic interaction of membrane lipid rafts and the cytoskeleton are discussed with respect to cell phenotype.

    PubMed  CAS  Google Scholar 

  15. Hazarika P, McCarty MF, Prieto VG, George S, Babu D, Koul D, et al. Up-regulation of Flotillin-2 is associated with melanoma progression and modulates expression of the thrombin receptor protease activated receptor 1. Cancer Res. 2004;64(20):7361–9.

    PubMed  CAS  Google Scholar 

  16. Li YC, Park MJ, Ye SK, Kim CW, Kim YN. Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents. Am J Pathol. 2006;168(4):1107–18. quiz 404–5.

    PubMed  CAS  PubMed Central  Google Scholar 

  17. Patra SK. Dissecting lipid raft facilitated cell signaling pathways in cancer. Biochim Biophys Acta. 2008;1785(2):182–206.

    PubMed  CAS  Google Scholar 

  18. Fedida-Metula S, Feldman B, Koshelev V, Levin-Gromiko U, Voronov E, Fishman D. Lipid rafts couple store-operated Ca2+ entry to constitutive activation of PKB/Akt in a Ca2+/calmodulin-, Src- and PP2A-mediated pathway and promote melanoma tumor growth. Carcinogenesis. 2012;33(4):740–50.

    PubMed  CAS  Google Scholar 

  19. Lasserre R, Guo XJ, Conchonaud F, Hamon Y, Hawchar O, Bernard AM, et al. Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation. Nat Chem Biol. 2008;4(9):538–47.

    PubMed  CAS  Google Scholar 

  20. Roy UK, Rial NS, Kachel KL, Gerner EW. Activated K-RAS increases polyamine uptake in human colon cancer cells through modulation of caveolar endocytosis. Mol Carcinog. 2008;47(7):538–53.

    PubMed  CAS  Google Scholar 

  21. Irwin ME, Mueller KL, Bohin N, Ge Y, Boerner JL. Lipid raft localization of EGFR alters the response of cancer cells to the EGFR tyrosine kinase inhibitor gefitinib. J Cell Physiol. 2011;226(9):2316–28.

    PubMed  CAS  PubMed Central  Google Scholar 

  22. George KS, Wu S. Lipid raft: a floating island of death or survival. Toxicol Appl Pharmacol. 2012;259(3):311–9.

    PubMed  CAS  PubMed Central  Google Scholar 

  23. Lacour S, Hammann A, Grazide S, Lagadic-Gossmann D, Athias A, Sergent O, et al. Cisplatin-induced CD95 redistribution into membrane lipid rafts of HT29 human colon cancer cells. Cancer Res. 2004;64(10):3593–8.

    PubMed  CAS  Google Scholar 

  24. Rebillard A, Tekpli X, Meurette O, Sergent O, LeMoigne-Muller G, Vernhet L, et al. Cisplatin-induced apoptosis involves membrane fluidification via inhibition of NHE1 in human colon cancer cells. Cancer Res. 2007;67(16):7865–74.

    PubMed  CAS  Google Scholar 

  25. Adachi S, Nagao T, Ingolfsson HI, Maxfield FR, Andersen OS, Kopelovich L, et al. The inhibitory effect of (−)-epigallocatechin gallate on activation of the epidermal growth factor receptor is associated with altered lipid order in HT29 colon cancer cells. Cancer Res. 2007;67(13):6493–501.

    PubMed  CAS  Google Scholar 

  26. Bacso Z, Bene L, Damjanovich L, Damjanovich S. INF-gamma rearranges membrane topography of MHC-I and ICAM-1 in colon carcinoma cells. Biochem Biophys Res Commun. 2002;290(2):635–40.

    PubMed  CAS  Google Scholar 

  27. Gelsomino G, Corsetto PA, Campia I, Montorfano G, Kopecka J, Castella B, et al. Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition. Mol Cancer. 2013;12:137. This cell culture based study provides evidence implicating omega 3 PUFA with lipid rafts and chemosensitivity.

    PubMed  Google Scholar 

  28. Ma DW, Seo J, Davidson LA, Callaway ES, Fan YY, Lupton JR, et al. n-3 PUFA alter caveolae lipid composition and resident protein localization in mouse colon. FASEB J. 2004;18(9):1040–2.

    PubMed  CAS  Google Scholar 

  29. Fan Y-Y, McMurray DN, Ly LH, Chapkin RS. Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts. J Nutr. 2003;133(6):1913–20.

  30. 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(2):466–71

  31. Shaikh SR, Cherezov V, Caffrey M, Soni SP, LoCascio D, Stillwell W, et al. Molecular organization of cholesterol in unsaturated phosphatidylethanolamines: X-ray diffraction and solid state 2H NMR reveal differences with phosphatidylcholines. J Am Chem Soc. 2006;128(16):5375–83.

    PubMed  CAS  Google Scholar 

  32. Brzustowicz MR, Cherezov V, Caffrey M, Stillwell W, Wassall SR. Molecular organization of cholesterol in polyunsaturated membranes: microdomain formation. Biophys J. 2002;82(1 Pt 1):285–98.

    PubMed  CAS  PubMed Central  Google Scholar 

  33. Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, et al. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res. 2009;69(8):3382–9.

    PubMed  CAS  PubMed Central  Google Scholar 

  34. Shaikh SR, Kinnun JJ, Leng X, Williams JA, Wassall SR. How polyunsaturated fatty acids modify molecular organization in membranes: insight from NMR studies of model systems. Biochim Biophys Acta. 2014. The effects of long chain polyunsaturated fatty acids with respect to the biophysical properties of membranes is discussed.

  35. Owen DM, Rentero C, Magenau A, Abu-Siniyeh A, Gaus K. Quantitative imaging of membrane lipid order in cells and organisms. Nat Protoc. 2012;7(1):24–35.

    CAS  Google Scholar 

  36. Gaus K, Zech T, Harder T. Visualizing membrane microdomains by Laurdan 2-photon microscopy. Mol Membr Biol. 2006;23(1):41–8.

    PubMed  CAS  Google Scholar 

  37. Kim W, Fan YY, Barhoumi R, Smith R, McMurray DN, Chapkin RS. n-3 polyunsaturated fatty acids suppress the localization and activation of signaling proteins at the immunological synapse in murine CD4+ T cells by affecting lipid raft formation. J Immunol. 2008;181(9):6236–43.

    PubMed  CAS  PubMed Central  Google Scholar 

  38. Kim W, Barhoumi R, McMurray DN, Chapkin RS. Dietary fish oil and DHA down-regulate antigen-activated CD4+ T-cells while promoting the formation of liquid-ordered mesodomains. Br J Nutr. 2014;111(2):254–60. Compelling evidence is provided indicating that n-3 PUFA from distinct dietary sources can be integrated into antigen activated CD4+ T-cells, resulting in the modulation of plasma membrane order and translocation of signaling kinases to the immunological synapse.

    PubMed  Google Scholar 

  39. Rockett BD, Teague H, Harris M, Melton M, Williams J, Wassall SR, et al. Fish oil increases raft size and membrane order of B cells accompanied by differential effects on function. J Lipid Res. 2012;53(4):674–85.

    PubMed  CAS  PubMed Central  Google Scholar 

  40. Zech T, Ejsing CS, Gaus K, de Wet B, Shevchenko A, Simons K, et al. Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR signalling. EMBO J. 2009;28(5):466–76.

    PubMed  CAS  PubMed Central  Google Scholar 

  41. Kim W, Khan NA, McMurray DN, Prior IA, Wang N, Chapkin RS. Regulatory activity of polyunsaturated fatty acids in T-cell signaling. Prog Lipid Res. 2010;49(3):250–61.

    PubMed  CAS  PubMed Central  Google Scholar 

  42. Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell. 2010;140(6):771–6.

    PubMed  CAS  Google Scholar 

  43. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99.

    PubMed  CAS  PubMed Central  Google Scholar 

  44. Chalaris A, Garbers C, Rabe B, Rose-John S, Scheller J. The soluble interleukin 6 receptor: generation and role in inflammation and cancer. Eur J Cell Biol. 2011;90(6–7):484–94.

    PubMed  CAS  Google Scholar 

  45. Prior IA, Muncke C, Parton RG, Hancock JF. Direct visualization of Ras proteins in spatially distinct cell surface microdomains. J Cell Biol. 2003;160(2):165–70.

    PubMed  CAS  PubMed Central  Google Scholar 

  46. Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys. 2004;59(2 Suppl):21–6.

    PubMed  CAS  Google Scholar 

  47. Montagut C, Dalmases A, Bellosillo B, Crespo M, Pairet S, Iglesias M, et al. Identification of a mutation in the extracellular domain of the epidermal growth factor receptor conferring cetuximab resistance in colorectal cancer. Nat Med. 2012;18(2):221–3.

    PubMed  CAS  Google Scholar 

  48. Pike LJ. Growth factor receptors, lipid rafts and caveolae: an evolving story. Biochim Biophys Acta. 2005;1746(3):260–73.

    PubMed  CAS  Google Scholar 

  49. Ringerike T, Blystad FD, Levy FO, Madshus IH, Stang E. Cholesterol is important in control of EGF receptor kinase activity but EGF receptors are not concentrated in caveolae. J Cell Sci. 2002;115(Pt 6):1331–40.

    PubMed  CAS  Google Scholar 

  50. Rogers KR, Kikawa KD, Mouradian M, Hernandez K, McKinnon KM, Ahwah SM, et al. Docosahexaenoic acid alters epidermal growth factor receptor-related signaling by disrupting its lipid raft association. Carcinogenesis. 2010;31(9):1523–30.

    PubMed  CAS  Google Scholar 

  51. Schley PD, Brindley DN, Field CJ. (n-3) PUFA alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells. J Nutr. 2007;137(3):548–53.

    PubMed  CAS  Google Scholar 

  52. Turk HF, Barhoumi R, Chapkin RS. Alteration of EGFR spatiotemporal dynamics suppresses signal transduction. PLoS One. 2012;7(6):e39682. DHA-induced alteration in both the lateral and subcellular localization of EGFR culminates in the suppression of downstream signal transduction, which has implications for the molecular basis of colon cancer prevention.

    PubMed  CAS  PubMed Central  Google Scholar 

  53. Stulnig TM, Huber J, Leitinger N, Imre EM, Angelisova P, Nowotny P, et al. Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition. J Biol Chem. 2001;276(40):37335–40.

    PubMed  CAS  Google Scholar 

  54. 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(32):28418–23.

    PubMed  CAS  Google Scholar 

  55. Eisenberg S, Laude AJ, Beckett AJ, Mageean CJ, Aran V, Hernandez-Valladares M, et al. The role of palmitoylation in regulating Ras localization and function. Biochem Soc Trans. 2013;41(1):79–83.

    PubMed  CAS  Google Scholar 

  56. Seo J, Barhoumi R, Johnson AE, Lupton JR, Chapkin RS. Docosahexaenoic acid selectively inhibits plasma membrane targeting of lipidated proteins. FASEB J. 2006;20(6):770–2.

    PubMed  CAS  Google Scholar 

  57. Krasinskas AM. EGFR signaling in colorectal carcinoma. Patholog Res Int. 2011;2011:932932.

    PubMed  PubMed Central  Google Scholar 

  58. Stephen AG, Esposito D, Bagni RK, McCormick F. Dragging ras back in the ring. Cancer Cell. 2014;25(3):272–81.

    PubMed  CAS  Google Scholar 

  59. Sawan C, Vaissiere T, Murr R, Herceg Z. Epigenetic drivers and genetic passengers on the road to cancer. Mutat Res. 2008;642(1–2):1–13.

    PubMed  CAS  Google Scholar 

  60. Cameron EE, Bachman KE, Myohanen S, Herman JG, Baylin SB. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet. 1999;21(1):103–7.

    PubMed  CAS  Google Scholar 

  61. Davis CD, Ross SA. Dietary components impact histone modifications and cancer risk. Nutr Rev. 2007;65(2):88–94.

    PubMed  Google Scholar 

  62. Ehrlich M. DNA hypomethylation in cancer cells. Epigenomics. 2009;1(2):239–59.

    PubMed  CAS  PubMed Central  Google Scholar 

  63. Kulis M, Esteller M. DNA methylation and cancer. Adv Genet. 2010;70:27–56.

    PubMed  Google Scholar 

  64. Mani S, Herceg Z. DNA demethylating agents and epigenetic therapy of cancer. Adv Genet. 2010;70:327–40.

    PubMed  CAS  Google Scholar 

  65. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705.

    PubMed  CAS  Google Scholar 

  66. Sawan C, Herceg Z. Histone modifications and cancer. Adv Genet. 2010;70:57–85.

    PubMed  CAS  Google Scholar 

  67. Steger DJ, Workman JL. Remodeling chromatin structures for transcription: what happens to the histones? Bioessays. 1996;18(11):875–84.

    PubMed  CAS  Google Scholar 

  68. Zhang K, Dent SY. Histone modifying enzymes and cancer: going beyond histones. J Cell Biochem. 2005;96(6):1137–48.

    PubMed  CAS  Google Scholar 

  69. Fabbri M, Calin GA. Epigenetics and miRNAs in human cancer. Adv Genet. 2010;70:87–99.

    PubMed  CAS  Google Scholar 

  70. Vandenboom Ii TG, Li Y, Philip PA, Sarkar FH. MicroRNA and cancer: tiny molecules with major implications. Curr Genomics. 2008;9(2):97–109.

    PubMed  PubMed Central  Google Scholar 

  71. Winter J, Diederichs S. MicroRNA biogenesis and cancer. Methods Mol Biol. 2011;676:3–22.

    PubMed  CAS  Google Scholar 

  72. Davidson LA, Nguyen DV, Hokanson RM, Callaway ES, Isett RB, Turner ND, et al. Chemopreventive n-3 polyunsaturated fatty acids reprogram genetic signatures during colon cancer initiation and progression in the rat. Cancer Res. 2004;64(18):6797–804.

    PubMed  CAS  Google Scholar 

  73. Davidson LA, Wang N, Ivanov I, Goldsby J, Lupton JR, Chapkin RS. Identification of actively translated mRNA transcripts in a rat model of early-stage colon carcinogenesis. Cancer Prev Res (Phila). 2009;2(11):984–94.

    CAS  Google Scholar 

  74. Piepoli A, Tavano F, Copetti M, Mazza T, Palumbo O, Panza A, et al. Mirna expression profiles identify drivers in colorectal and pancreatic cancers. PLoS One. 2012;7(3):e33663.

    PubMed  CAS  PubMed Central  Google Scholar 

  75. Slaby O, Svoboda M, Michalek J, Vyzula R. MicroRNAs in colorectal cancer: translation of molecular biology into clinical application. Mol Cancer. 2009;8:102.

    PubMed  PubMed Central  Google Scholar 

  76. Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M, et al. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 2007;72(5–6):397–402.

    PubMed  CAS  Google Scholar 

  77. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27(15):2128–36.

    PubMed  CAS  Google Scholar 

  78. Wang P, Zou F, Zhang X, Li H, Dulak A, Tomko Jr RJ, et al. microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells. Cancer Res. 2009;69(20):8157–65.

    PubMed  CAS  PubMed Central  Google Scholar 

  79. Kim YJ, Hwang SJ, Bae YC, Jung JS. MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue. Stem Cells. 2009;27(12):3093–102.

    PubMed  CAS  Google Scholar 

  80. Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, Colburn NH, et al. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene. 2008;27(31):4373–9.

    PubMed  CAS  Google Scholar 

  81. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647–58.

    PubMed  CAS  Google Scholar 

  82. Shi L, Chen J, Yang J, Pan T, Zhang S, Wang Z. MiR-21 protected human glioblastoma U87MG cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 activity. Brain Res. 2010;1352:255–64.

    PubMed  CAS  Google Scholar 

  83. Song B, Wang C, Liu J, Wang X, Lv L, Wei L, et al. MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression. J Exp Clin Cancer Res. 2010;29:29.

    PubMed  CAS  PubMed Central  Google Scholar 

  84. Wickramasinghe NS, Manavalan TT, Dougherty SM, Riggs KA, Li Y, Klinge CM. Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells. Nucleic Acids Res. 2009;37(8):2584–95.

    PubMed  CAS  PubMed Central  Google Scholar 

  85. Zhang Z, Li Z, Gao C, Chen P, Chen J, Liu W, et al. miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Invest. 2008;88(12):1358–66.

    PubMed  CAS  Google Scholar 

  86. Zhou X, Zhang J, Jia Q, Ren Y, Wang Y, Shi L, et al. Reduction of miR-21 induces glioma cell apoptosis via activating caspase 9 and 3. Oncol Rep. 2010;24(1):195–201.

    PubMed  CAS  Google Scholar 

  87. Kolar SS, Barhoumi R, Callaway ES, Fan YY, Wang N, Lupton JR, et al. 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(5):G935–43.

    PubMed  CAS  Google Scholar 

  88. Kolar SS, Barhoumi R, Lupton JR, Chapkin RS. Docosahexaenoic acid and butyrate synergistically induce colonocyte apoptosis by enhancing mitochondrial Ca2+ accumulation. Cancer Res. 2007;67(11):5561–8.

    PubMed  CAS  Google Scholar 

  89. Vanamala J, Glagolenko A, Yang P, Carroll RJ, Murphy ME, Newman RA, et al. Dietary fish oil and pectin enhance colonocyte apoptosis in part through suppression of PPARdelta/PGE2 and elevation of PGE3. Carcinogenesis. 2008;29(4):790–6.

    PubMed  CAS  PubMed Central  Google Scholar 

  90. Chen Y, Shu W, Chen W, Wu Q, Liu H, Cui G. Curcumin, both histone deacetylase and p300/CBP-specific inhibitor, represses the activity of nuclear factor kappa B and Notch 1 in Raji cells. Basic Clin Pharmacol Toxicol. 2007;101(6):427–33.

    PubMed  CAS  Google Scholar 

  91. Fu S, Kurzrock R. Development of curcumin as an epigenetic agent. Cancer. 2010;116(20):4670–6.

    PubMed  CAS  Google Scholar 

  92. Liu HL, Chen Y, Cui GH, Zhou JF. Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation. Acta Pharmacol Sin. 2005;26(5):603–9.

    PubMed  CAS  Google Scholar 

  93. Reuter S, Gupta SC, Park B, Goel A, Aggarwal BB. Epigenetic changes induced by curcumin and other natural compounds. Genes Nutr. 2011;6(2):93–108.

    PubMed  CAS  PubMed Central  Google Scholar 

  94. Wu Q, Chen Y, Li X. HDAC1 expression and effect of curcumin on proliferation of Raji cells. J Huazhong Univ Sci Technolog Med Sci. 2006;26(2):199–201. 10.

    PubMed  Google Scholar 

  95. Ye MX, Li Y, Yin H, Zhang J. Curcumin: updated molecular mechanisms and intervention targets in human lung cancer. Int J Mol Sci. 2012;13(3):3959–78.

    PubMed  CAS  PubMed Central  Google Scholar 

  96. Kelkel M, Jacob C, Dicato M, Diederich M. Potential of the dietary antioxidants resveratrol and curcumin in prevention and treatment of hematologic malignancies. Molecules. 2010;15(10):7035–74.

    PubMed  CAS  Google Scholar 

  97. Teiten MH, Eifes S, Reuter S, Duvoix A, Dicato M, Diederich M. Gene expression profiling related to anti-inflammatory properties of curcumin in K562 leukemia cells. Ann N Y Acad Sci. 2009;1171:391–8.

    PubMed  CAS  Google Scholar 

  98. Reuter S, Charlet J, Juncker T, Teiten MH, Dicato M, Diederich M. Effect of curcumin on nuclear factor kappaB signaling pathways in human chronic myelogenous K562 leukemia cells. Ann N Y Acad Sci. 2009;1171:436–47.

    PubMed  CAS  Google Scholar 

  99. Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 2008;269(2):199–225.

    PubMed  CAS  Google Scholar 

  100. Jia Q, Ivanov I, Zlatev ZZ, Alaniz RC, Weeks BR, Callaway ES, et al. Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice. Br J Nutr. 2011;106(4):519–29.

    PubMed  CAS  Google Scholar 

  101. Fenton JI, McCaskey SJ. Curcumin and docosahexaenoic acid block insulin-induced colon carcinoma cell proliferation. Prostaglandins Leukot Essent Fatty Acids. 2013;88(3):219–26.

    PubMed  CAS  Google Scholar 

  102. Siddiqui RA, Harvey KA, Walker C, Altenburg J, Xu Z, Terry C, et al. Characterization of synergistic anti-cancer effects of docosahexaenoic acid and curcumin on DMBA-induced mammary tumorigenesis in mice. BMC Cancer. 2013;13:418.

    PubMed  PubMed Central  Google Scholar 

  103. Bordonaro M, Lazarova DL, Sartorelli AC. Butyrate and Wnt signaling: a possible solution to the puzzle of dietary fiber and colon cancer risk? Cell Cycle. 2008;7(9):1178–83.

    PubMed  CAS  Google Scholar 

  104. Fan YY, Davidson LA, Callaway ES, Goldsby JS, Chapkin RS. Differential effects of 2- and 3-series E-prostaglandins on in vitro expansion of Lgr5+ colonic stem cells. Carcinogenesis. 2014;35(3):606–12. Relative to arachidonic acid-derived PGE2, a known promoter of colon tumorigenesis, eicosapentaenoic acid-derived PGE3 has diminished ability to support colonic stem cell expansion in mouse colonic organoids.

    PubMed  CAS  Google Scholar 

  105. Fujise T, Iwakiri R, Kakimoto T, Shiraishi R, Sakata Y, Wu B, et al. 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(4):G1150–6.

    PubMed  CAS  Google Scholar 

  106. Liu Z, Choi SW, Crott JW, Keyes MK, Jang H, Smith DE, et al. Mild depletion of dietary folate combined with other B vitamins alters multiple components of the Wnt pathway in mouse colon. J Nutr. 2007;137(12):2701–8.

    PubMed  CAS  Google Scholar 

  107. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17(1):9–26.

    PubMed  CAS  PubMed Central  Google Scholar 

  108. Willis ND, Przyborski SA, Hutchison CJ, Wilson RG. Colonic and colorectal cancer stem cells: progress in the search for putative biomarkers. J Anat. 2008;213(1):59–65.

    PubMed  PubMed Central  Google Scholar 

  109. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38.

    PubMed  Google Scholar 

  110. Ning Y, Wang L, Giovannucci EL. A quantitative analysis of body mass index and colorectal cancer: findings from 56 observational studies. Obes Rev. 2010;11(1):19–30.

    PubMed  CAS  Google Scholar 

  111. Ashktorab H, Paydar M, Yazdi S, Namin HH, Sanderson A, Begum R, et al. BMI and the risk of colorectal adenoma in African-Americans. Obesity (Silver Spring). 2014;22(5):1387–91.

    Google Scholar 

  112. Endo H, Hosono K, Fujisawa T, Takahashi H, Sugiyama M, Yoneda K, et al. Involvement of JNK pathway in the promotion of the early stage of colorectal carcinogenesis under high-fat dietary conditions. Gut. 2009;58(12):1637–43.

    PubMed  CAS  Google Scholar 

  113. Olivo-Marston SE, Hursting SD, Perkins SN, Schetter A, Khan M, Croce C, et al. Effects of calorie restriction and diet-induced obesity on murine colon carcinogenesis, growth and inflammatory factors, and microRNA expression. PLoS One. 2014;9(4):e94765. Diet-induced obesity and the suppressive effects of calorie restriction on colon carcinogenesis are associated with alterations in non-coding microRNAs.

    PubMed  PubMed Central  Google Scholar 

  114. Sikalidis AK, Fitch MD, Fleming SE. Diet induced obesity increases the risk of colonic tumorigenesis in mice. Pathol Oncol Res. 2013;19(4):657–66.

    PubMed  CAS  Google Scholar 

  115. Johnson AR, Milner JJ, Makowski L. The inflammation highway: metabolism accelerates inflammatory traffic in obesity. Immunol Rev. 2012;249(1):218–38.

    PubMed  CAS  PubMed Central  Google Scholar 

  116. Karastergiou K, Mohamed-Ali V. The autocrine and paracrine roles of adipokines. Mol Cell Endocrinol. 2010;318(1–2):69–78.

    PubMed  CAS  Google Scholar 

  117. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117(1):175–84.

    PubMed  CAS  PubMed Central  Google Scholar 

  118. Lumeng CN, Deyoung SM, Bodzin JL, Saltiel AR. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes. 2007;56(1):16–23.

    PubMed  CAS  Google Scholar 

  119. Monk JM, Hou TY, Turk HF, Weeks B, Wu C, McMurray DN, et al. Dietary n-3 polyunsaturated fatty acids (PUFA) decrease obesity-associated Th17 cell-mediated inflammation during colitis. PLoS One. 2012;7(11):e49739. n-3 PUFA suppress Th1/Th17 cells and inflammatory macrophage subsets and reconfigure the inflammatory gene expression profile in diverse tissue sites in obese mice following the induction of colitis.

    PubMed  CAS  PubMed Central  Google Scholar 

  120. Janakiram NB, Rao CV. The role of inflammation in colon cancer. Adv Exp Med Biol. 2014;816:25–52.

    PubMed  Google Scholar 

  121. Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005;5(10):749–59.

    PubMed  CAS  Google Scholar 

  122. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.

    PubMed  CAS  Google Scholar 

  123. Famulla S, Lamers D, Hartwig S, Passlack W, Horrighs A, Cramer A, et al. Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cells. Int J Obes (Lond). 2011;35(6):762–72.

    CAS  Google Scholar 

  124. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257(1):79–83.

    PubMed  CAS  Google Scholar 

  125. DeClercq V, Enns JE, Yeganeh A, Taylor CG, Zahradka P. Modulation of cardiovascular function by adipokines. Cardiovasc Hematol Disord Drug Targets. 2013;13(1):59–72.

    PubMed  CAS  Google Scholar 

  126. Shetty S, Kusminski CM, Scherer PE. Adiponectin in health and disease: evaluation of adiponectin-targeted drug development strategies. Trends Pharmacol Sci. 2009;30(5):234–9.

    PubMed  CAS  Google Scholar 

  127. Yamauchi T, Kadowaki T. Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases. Int J Obes (Lond). 2008;32 Suppl 7:S13–8.

    CAS  Google Scholar 

  128. Otake S, Takeda H, Fujishima S, Fukui T, Orii T, Sato T, et al. Decreased levels of plasma adiponectin associated with increased risk of colorectal cancer. World J Gastroenterol. 2010;16(10):1252–7.

    PubMed  CAS  PubMed Central  Google Scholar 

  129. Wei EK, Giovannucci E, Fuchs CS, Willett WC, Mantzoros CS. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst. 2005;97(22):1688–94.

    PubMed  CAS  Google Scholar 

  130. Yamaji T, Iwasaki M, Sasazuki S, Tsugane S. Interaction between adiponectin and leptin influences the risk of colorectal adenoma. Cancer Res. 2010;70(13):5430–7.

    PubMed  CAS  Google Scholar 

  131. Fenton JI, Birmingham JM. Adipokine regulation of colon cancer: adiponectin attenuates interleukin-6-induced colon carcinoma cell proliferation via STAT-3. Mol Carcinog. 2010;49(7):700–9.

    PubMed  CAS  PubMed Central  Google Scholar 

  132. Fujisawa T, Endo H, Tomimoto A, Sugiyama M, Takahashi H, Saito S, et al. Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition. Gut. 2008;57(11):1531–8.

    PubMed  CAS  PubMed Central  Google Scholar 

  133. Kim AY, Lee YS, Kim KH, Lee JH, Lee HK, Jang SH, et al. Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation. Mol Endocrinol. 2010;24(7):1441–52.

    PubMed  CAS  Google Scholar 

  134. Moon HS, Liu X, Nagel JM, Chamberland JP, Diakopoulos KN, Brinkoetter MT, et al. Salutary effects of adiponectin on colon cancer: in vivo and in vitro studies in mice. Gut. 2013;62(4):561–70. Adipose-derived adipokines are directly implicated in colon cancer risk.

    PubMed  CAS  Google Scholar 

  135. Pan H, Guo J, Su Z. Advances in understanding the interrelations between leptin resistance and obesity. Physiol Behav. 2014;130:157–69.

    PubMed  CAS  Google Scholar 

  136. Chia VM, Newcomb PA, Lampe JW, White E, Mandelson MT, McTiernan A, et al. Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev. 2007;16(12):2697–703.

    PubMed  CAS  Google Scholar 

  137. Birmingham JM, Busik JV, Hansen-Smith FM, Fenton JI. Novel mechanism for obesity-induced colon cancer progression. Carcinogenesis. 2009;30(4):690–7.

    PubMed  CAS  PubMed Central  Google Scholar 

  138. Endo H, Hosono K, Uchiyama T, Sakai E, Sugiyama M, Takahashi H, et al. Leptin acts as a growth factor for colorectal tumours at stages subsequent to tumour initiation in murine colon carcinogenesis. Gut. 2011;60(10):1363–71.

    PubMed  CAS  Google Scholar 

  139. Padidar S, Farquharson AJ, Williams LM, Kelaiditi E, Hoggard N, Arthur JR, et al. Leptin up-regulates pro-inflammatory cytokines in discrete cells within mouse colon. J Cell Physiol. 2011;226(8):2123–30.

    PubMed  CAS  Google Scholar 

  140. Yamaji T, Iwasaki M, Sasazuki S, Tsugane S. Interaction between adiponectin and leptin influences the risk of colorectal adenoma. Cancer Res. 2010;70(13):5430–7.

    PubMed  CAS  Google Scholar 

  141. Fenton JI, Birmingham JM, Hursting SD, Hord NG. Adiponectin blocks multiple signaling cascades associated with leptin-induced cell proliferation in Apc Min/+colon epithelial cells. Int J Cancer. 2008;122(11):2437–45.

    PubMed  CAS  Google Scholar 

  142. Li Y, Wang L, Pappan L, Galliher-Beckley A, Shi J. IL-1beta promotes stemness and invasiveness of colon cancer cells through Zeb1 activation. Mol Cancer. 2012;11:87.

    PubMed  PubMed Central  Google Scholar 

  143. Wang L, Liu Z, Li Y, Pappan L, Galliher-Beckley A, Shi J. Pro-inflammatory cytokine interleukin-1beta promotes the development of intestinal stem cells. Inflamm Res. 2012;61(10):1085–92.

    PubMed  CAS  Google Scholar 

  144. Hyun YS, Han DS, Lee AR, Eun CS, Youn J, Kim HY. Role of IL-17A in the development of colitis-associated cancer. Carcinogenesis. 2012;33(4):931–6.

    PubMed  CAS  Google Scholar 

  145. Hillenbrand A, Fassler J, Huber N, Xu P, Henne-Bruns D, Templin M et al. Changed adipocytokine concentrations in colorectal tumor patients and morbidly obese patients compared to healthy controls. BMC cancer. 2012;12:545–2407–12–545.

  146. Itariu BK, Zeyda M, Hochbrugger EE, Neuhofer A, Prager G, Schindler K, et al. Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial. Am JClin Nutr. 2012;96(5):1137–49. Treatment with long-chain n-3 PUFAs favorably modulated adipose tissue and systemic inflammation in severely obese non-diabetic patients and improved lipid metabolism.

    CAS  Google Scholar 

  147. Jilkova ZM, Hensler M, Medrikova D, Janovska P, Horakova O, Rossmeisl M, et al. Adipose tissue-related proteins locally associated with resolution of inflammation in obese mice. Int J Obes (Lond). 2014;38(2):216–23.

    CAS  Google Scholar 

  148. Kuda O, Jelenik T, Jilkova Z, Flachs P, Rossmeisl M, Hensler M, et al. n-3 fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet. Diabetologia. 2009;52(5):941–51.

    PubMed  CAS  Google Scholar 

  149. Jia Q, Lupton JR, Smith R, Weeks BR, Callaway E, Davidson LA, et al. Reduced colitis-associated colon cancer in fat-1 (n-3 fatty acid desaturase) transgenic mice. Cancer Res. 2008;68(10):3985–91.

    PubMed  CAS  PubMed Central  Google Scholar 

  150. Nowak J, Weylandt KH, Habbel P, Wang J, Dignass A, Glickman JN, et al. Colitis-associated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids. Carcinogenesis. 2007;28(9):1991–5.

    PubMed  CAS  Google Scholar 

  151. 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(5):1927–33.

    PubMed  CAS  Google Scholar 

  152. D’Archivio M, Scazzocchio B, Giammarioli S, Fiani ML, Vari R, Santangelo C, et al. Omega 3-PUFAs exert anti-inflammatory activity in visceral adipocytes from colorectal cancer patients. PLoS One. 2013;8(10):e77432. Adipocyte dysfunction occurs in colon cancer patients creating a pro-inflammatory environment that might influence cancer development. The protective potential of DHA in re-establishing the equilibrium between pro- and anti-inflammatory factors is documented.

    PubMed  PubMed Central  Google Scholar 

  153. Chapkin RS, McMurray DN, Lupton JR. Colon cancer, fatty acids and anti-inflammatory compounds. Curr Opin Gastroenterol. 2007;23(1):48–54.

    PubMed  CAS  Google Scholar 

  154. Cheng J, Ogawa K, Kuriki K, Yokoyama Y, Kamiya T, Seno K, et al. Increased intake of n-3 polyunsaturated fatty acids elevates the level of apoptosis in the normal sigmoid colon of patients polypectomized for adenomas/tumors. Cancer Lett. 2003;193(1):17–24.

    PubMed  CAS  Google Scholar 

  155. Cockbain AJ. Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer. Gut. 2012;61(1):135–49.

    PubMed  CAS  Google Scholar 

  156. Courtney ED. Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas. Int J Color Dis. 2007;22(7):765–76.

    CAS  Google Scholar 

  157. Turk HF, Monk JM, Fan YY, Callaway ES, Weeks B, Chapkin RS. Inhibitory effects of omega-3 fatty acids on injury induced epidermal growth factor transactivation contribute to delayed wound healing. Am J Physiol Cell Physiol. 2013;304(9):C905–17.

    PubMed  CAS  PubMed Central  Google Scholar 

  158. Lien EL. Toxicology and safety of DHA. Prostaglandins Leukot Essent Fatty Acids. 2009;81(2–3):125–32.

    PubMed  CAS  Google Scholar 

  159. Bell GA, Kantor ED, Lampe JW, Kristal AR, Heckbert SR, White E. Intake of long-chain omega-3 fatty acids from diet and supplements in relation to mortality. Am J Epidemiol. 2014;179(6):710–20.

    PubMed  Google Scholar 

  160. Hou TY, Monk JM, Fan YY, Barhoumi R, Chen YQ, Rivera GM, et al. n-3 polyunsaturated fatty acids suppress phosphatidylinositol 4,5-bisphosphate-dependent actin remodelling during CD4+ T-cell activation. Biochem J. 2012;443(1):27–37. Cogent evidence demonstrates for the first time that DHA modulates PI(4,5)P2-dependent actin remodeling by decreasing steady-state PI(4,5)P2 levels. These findings highlight a novel modality by which n-3 PUFA influence membrane organization, thereby modulating biological responses.

    PubMed  CAS  Google Scholar 

  161. Mate S, Busto JV, Garcia-Arribas AB, Sot J, Vazquez R, Herlax V, et al. N-Nervonoylsphingomyelin (c24:1) prevents lateral heterogeneity in cholesterol-containing membranes. Biophys J. 2014;106(12):2606–16.

    PubMed  CAS  Google Scholar 

  162. Rajamoorthi K, Petrache HI, McIntosh TJ, Brown MF. Packing and viscoelasticity of polyunsaturated omega-3 and omega-6 lipid bilayers as seen by (2)H NMR and X-ray diffraction. J Am Chem Soc. 2005;127(5):1576–88.

    PubMed  CAS  Google Scholar 

  163. Shah MS, Schwartz SL, Zhao C, Davidson LA, Zhou B, Lupton JR, et al. Integrated microRNA and mRNA expression profiling in a rat colon carcinogenesis model: effect of a chemo-protective diet. Physiol Genomics. 2011;43(10):640–54.

    PubMed  CAS  PubMed Central  Google Scholar 

  164. Gil-Zamorano J, Martin R, Daimiel L, Richardson K, Giordano E, Nicod N, et al. Docosahexaenoic acid modulates the enterocyte Caco-2 cell expression of microRNAs involved in lipid metabolism. J Nutr. 2014;144(5):575–85.

    PubMed  CAS  Google Scholar 

  165. Sun H, Meng X, Han J, Zhang Z, Wang B, Bai X, et al. Anti-cancer activity of DHA on gastric cancer—an in vitro and in vivo study. Tumour Biol. 2013;34(6):3791–800.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the American Institute for Cancer Research (AICR); Cancer Prevention and Research Institute of Texas (CPRIT); National Institutes of Health grants CA129444, CA168312, and P30ES023512; and USDA–NIFA Grant Designing Foods for Health 2010-34402-20875. The authors would also like to thank Tim Hou for formatting assistance.

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

Robert S. Chapkin, Vanessa DeClercq, Eunjoo Kim, Natividad Roberto Fuentes, and Yang-Yi Fan declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, TX, 77843, USA

    Robert S. Chapkin, Vanessa DeClercq, Eunjoo Kim, Natividad Roberto Fuentes & Yang-Yi Fan

  2. Center for Translational Environmental Health Research, Texas A&M University, College Station, TX, 77843, USA

    Robert S. Chapkin

  3. Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA

    Robert S. Chapkin, Vanessa DeClercq & Yang-Yi Fan

  4. Biochemistry & Biophysics, Texas A&M University, College Station, TX, 77843, USA

    Robert S. Chapkin

  5. Molecular & Cellular Medicine, Texas A&M University, College Station, TX, 77843, USA

    Eunjoo Kim

  6. Faculty of Toxicity, Texas A&M University, College Station, TX, 77843, USA

    Robert S. Chapkin & Natividad Roberto Fuentes

Authors
  1. Robert S. Chapkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vanessa DeClercq
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eunjoo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Natividad Roberto Fuentes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yang-Yi Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert S. Chapkin.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chapkin, R.S., DeClercq, V., Kim, E. et al. Mechanisms by Which Pleiotropic Amphiphilic n−3 PUFA Reduce Colon Cancer Risk. Curr Colorectal Cancer Rep 10, 442–452 (2014). https://doi.org/10.1007/s11888-014-0241-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11888-014-0241-6

Keywords

Search

Navigation