Hostname: page-component-848d4c4894-75dct Total loading time: 0 Render date: 2024-05-26T21:41:10.329Z Has data issue: false hasContentIssue false

Kill and cure: dietary augmentation of immune defences against colon cancer

Published online by Cambridge University Press:  28 February 2007

Fiona Armstrong*
Human Nutrition Research Centre, Department of Biological and Nutritional Sciences, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK
J. C. Mathers
Human Nutrition Research Centre, Department of Biological and Nutritional Sciences, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK
*Corresponding author: Ms Fiona Armstrong, fax +44 (0) 191 222 8684, email
Rights & Permissions [Opens in a new window]


Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

At its most fundamental, cancer is a genetic disease resulting from inherited or acquired mutations in tumour suppressor genes and proto-oncogenes. Environmental factors, including ingested food components, interact with genetic inheritance to determine individual cancer risk. There is growing evidence that the immune system exerts selective pressure during neoplastic development. Tumour cells that evade this immunosurveillance because they are non-antigenic or because they defend themselves successfully against immune attack have a survival advantage. Effective chemopreventative agents will include dietary components that enhance the immune system’s ability to identify transformed cells and to target them for apoptosis.

Postgraduate Symposium
Copyright © The Nutrition Society 2000


Behrens, J, von, Kries JP, Kühl, M, Bruhn, L, Wedlich, D, Grosschedll, R & Birchmeier, W (1996) Functional interaction of β-catenin with the transcription factor LEF-1. Nature 382, 638642.CrossRefGoogle ScholarPubMed
Belch, JJF & Muir, A (1998) n-3 and n-6 Essential fatty acids in rheumatoid arthritis and other rheumatic conditions. Proceedings of the Nutrition Society 57, 563569.CrossRefGoogle ScholarPubMed
Berry, J, Green, BJ & Matheson, DS (1987) Modulation of natural killer cell activity by tamoxifen in stage 1 post-menopausal breast cancer. European Journal of Cancer Clinics and Oncology 23, 517520.CrossRefGoogle ScholarPubMed
Birkeland, SA, Storm, SA, Lamm, LU, Barlow, I, Blohme, I, Forsberg, B, Eklund, B, Fjeldborg, O, Friedberg, M, Frodin, L, Glattre, E, Halvorsen, S, Holm, NV, Jakobsen, A, Jorgensen, HE, Ladefoged, J, Lindholm, T, Lundgren, G & Pukkala, E (1995) Cancer risk after renal-transplantation in the Nordic countries, 1964–1986. International Journal of Cancer 60, 183189.Google Scholar
Bonnotte, B, Favre, N, Reveneau, S, Micheau, O, Droin, N, Garrido, C, Fontana, A, Chauffert, B, Solary, E & Martin, F (1998) Cancer cell sensitization to Fas-mediated apoptosis by sodium butyrate. Cell Death and Differentiation 5, 480487.Google Scholar
Browne, SJ, Williams, AC, Hague, A, Butt, AJ & Paraskeva, C (1994) Loss of APC protein expressed by human colonic epithelial cells and the appearance of a specific low-molecular weight form is associated with apoptosis in vitro. International Journal of Cancer 59, 5664.Google Scholar
Burn, J, Chapman, PD, Bishop, DT & Mathers, J (1998) Diet and cancer prevention: the Concerted Action Polyp Prevention (CAPP) Studies. Proceedings of the Nutrition Society 57, 183186.Google Scholar
Burnet, FM (1976) Immunology, Aging and Cancer.San Francisco, CA: W.H. Freeman and Co.Google Scholar
Calder, PC (1998) Dietary fatty acids and lymphocyte functions. Proceedings of the Nutrition Society 57, 487502.Google Scholar
Cave, WT (1991) Dietary n-3 (ω-3) polyunsaturated fatty acid effects on animal tumorigenesis. FASEB Journal 5, 21602165.CrossRefGoogle ScholarPubMed
Cheng, B-Q, Trimble, RP, Illman, RJ, Stone, BA & Topping, DL (1987) Comparative effects of dietary wheat bran and its morphological components (aleurone and pericarp-seed coat) on volatile fatty acid concentrations in the rat. British Journal of Nutrition 57, 6986.Google Scholar
Cuisset, L, Tichonicky, L & Delpech, M (1998) A protein phosphatase is involved in the inhibition of histone deacetylation by sodium butyrate. Biochemical and Biophysical Research Communications 246, 760764.Google Scholar
Currie, G (1980) Cancer and the Immune Response. 2nd ed. London: Edward Arnold.Google Scholar
D'Argenio, G, Cosenza, V, Cave, MD, Iovini, P, Valle, ND, Lambardi, G & Mazzacca, G (1996) Butyrate enemas in experimental colitis and protection against large bowel cancer in a rat model. Gastroenterology 110, 17271734.Google Scholar
Department of Health (1998) Nutritional Aspects of the Development of Cancer. Report on Health and Social Subjects no. 48. London: The Stationery OfficeGoogle Scholar
Dove, WF, Clipson, L, Gould, KA, Luongo, C, Marshall, DJ, Moser, AR, Newton, MA & Jacoby, RF (1997) Intestinal neoplasia in the ApcMin mouse: independence from the microbial and natural killer (beige locus) status. Cancer Research 57, 812814.Google Scholar
Dudley, ME, Sundberg, JP & Roopenian, DC (1996) Frequency and histological appearance of adenomas in multiple intestinal neoplasia mice are unaffected by severe combined immunodeficiency (scid) mutation. International Journal of Cancer 65, 249253.3.0.CO;2-7>CrossRefGoogle ScholarPubMed
Ferguson, A (1993) Nutrition and the immune system Human Nutrition and Dietetics, 9th ed. 685700. [Garrow, JS & James, WPT, editors]. Edinburgh: Churchill Livingstone.Google Scholar
Fernandes, G, Troyer, DA & Jolly, CA (1998) The effects of dietary lipids on gene expression and apoptosis. Proceedings of the Nutrition Society 57, 543550.Google Scholar
Fisher, B, Constantino, JP, Wickerman, L, Redmond, CK, Kavanah, M, Cronin, WM, Vogel, V, Robidoux, A, Dimitrou, N, Atkins, J, Daly, M, Weinands, S, Tan, Chui E, Ford, L & Wolmark, N (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. Journal of the National Cancer Institute 90, 13711388.Google Scholar
Fodde, R, Edelman, W, Yang, K, van Leeuwan, C, Carlson, C, Renault, B, Breukel, C, Alt, E, Lipkin, M, Khan, PM & Kucherlapati, R (1994) A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proceedings of the National Academy of Sciences USA 91, 89698973.Google Scholar
Fox, JG, Dangler, CA, Whary, MT, Edelman, W, Kucherlapati, R & Wang, TC (1997) Mice carrying a truncated Apc gene have diminished gastric epithelial proliferation, gastric inflammation and humoral immunity in response to Helicobacter felis infection. Cancer Research 57, 39723978.Google Scholar
Griffin, TS & Ferguson, TA (1997) The role of FasL-induced apoptosis in immune privilege. Immunology Today 18, 240244.Google Scholar
Grimble, RF (1998) Dietary lipids and the inflammatory response. Proceedings of the Nutrition Society 57, 535542.Google Scholar
Hague, A, Butt, AJ & Paraskeva, C (1996) The role of butyrate in intestinal colonic epithelial cells: an energy source or inducer of differentiation and apoptosis? Proceedings of the Nutrition Society 55, 937943.Google Scholar
Hermiston, ML & Gordon, JI (1995) Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science 270, 12031207.Google Scholar
Ilyas, M, Straub, J, Tomlinson, IPM & Bodmer, WF (1999) Genetic pathways in colorectal and other cancers. European Journal of Cancer 35, 335351.CrossRefGoogle ScholarPubMed
Jacoby, RF, Marshall, DJ, Newton, MA, Novakovic, K, Tutsch, K, Cole, C, Lubet, RA, Kelloff, GJ, Verma, A, Moser, AR & Dove, WF (1996) Chemoprevention of spontaneous intestinal adenomas in the Apc Min mouse model by the nonsteroidal anti-inflammatory drug piroxicam. Cancer Research 55, 44794485.Google Scholar
Janeway, CA Jr, Travers, P, Walport, M & Capra, JD (1999) Immunobiology. The Immune System in Health and Disease, 4th ed..London: Current Biology Publications.Google Scholar
Key, FB & Mathers, JC (1993) Gastrointestinal responses of rats fed on white and wholemeal breads: complex carbohydrate digestibility and the influence of dietary fat content. British Journal of Nutrition 69, 481495.Google Scholar
Kleibeuker, JH, Nagengast, FM & van der, Meer R (1996) Carcinogenesis in the colon Prevention and Early Detection of Colorectal Cancer 4562. [GYoung, p, Rozen, p & Levin, B, editors]. London: WB Saunders Co. Ltd.Google Scholar
Kruh, J, Tichonicky, L & Defer, N (1994) Effect of butyrate on gene expression Short Chain Fatty Acids 135147. [Binder, HJ, Cummings, JH & Soergel, K, editors]. Lancaster: Kluwer Academic Publications.Google Scholar
Lane, PW & Murphy, ED (1972) Susceptibility to spontaneous pneumonitis in an inbred strain of beige and satin mice. Genetics 72, 451460.CrossRefGoogle Scholar
Lim, BO, Yamada, K, Nonaka, M, Kuramoto, Y, Hung, P & Sugano, M (1997) Dietary fibre modulates indices of intestinal immune function in rats Journal of Nutrition 127, 663667.Google Scholar
McIntyre, A, Gibson, PR & Young, GP (1993) Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut 34, 386391.Google Scholar
Mathers, JC & FotsoTagny, J-M (1994) Diurnal changes in large-bowel metabolism: short-chain fatty acids and transit time in rats fed on wheat bran. British Journal of Nutrition 71, 209222.Google Scholar
Medina, V, Edmonds, B, Young, GP, James, R, Appleton, S & Zalewski, PD (1997) Induction of caspase-3 protease activity and apoptosis by butyrate and trichostatin A (inhibitors of histone deacetylase): Dependence on protein synthesis and synergy with a mitochondrial/cytochrome c-dependent pathway. Cancer Research 57, 36973707.Google Scholar
Möller, G & Möller, E (1975) Considerations of some current concepts in cancer research. Journal of the National Cancer Institute 55, 755759.Google Scholar
Moser, AR, Pitot, HC & Dove, WF (1990) A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247, 322324.Google Scholar
O'Connell, J, Bennett, MW, O'Sullivan, GC, Collins, JK & Shanahan, F (1999) Fas counter-attack – the best form of defense? Nature Medicine 5, 267268.CrossRefGoogle ScholarPubMed
O'Connell, J, O'Sullivan, GC, Collins, JK & Shanahan, F (1996) The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. Journal of Experimental Medicine 184, 10751082.Google Scholar
Oshima, M, Takahashi, M, Oshima, H, Tsutsumi, M, Yazawa, K, Sugimura, T, Nishimura, S, Wakabayashi, K & Taketo, MM (1995) Effects of docosahexaenoic acid (DHA) on intestinal polyp development in Apc Δ716 knockout mice. Carcinogenesis 16, 26052607.CrossRefGoogle Scholar
Perrin, P, Cassagnau, E, Burg, C, Patry, Y, Vavasseur, F, Harb, J, Le, Pendu J, Douillard, J-Y, Galmiche, J-P, Bornet, F & Meflah, K (1994) An interleukin 2/sodium butyrate combination as immunotherapy for rat colon cancer peritoneal carcinomatosis. Gastroenterology 107, 13971708.Google Scholar
Pitti, RM, Marsters, SA, Lawrence, DA, Roy, M, Kischkel, FC, Dowd, P, Huang, A, Donahue, CJ, Sherwood, SW, Baldwin, DT, Godowski, PJ, Wood, WI, Gurney, AL, Hillan, KJ, Cohen, RL, Goddard, AD, Botstein, D & Ashkenazi, A (1998) Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 396, 699703.Google Scholar
Reale, MA & Fearon, ER (1996) Gene defects in colorectal carcinogenesis Prevention and Early Detection of Colorectal Cancer 6386. [Young, GP, Rozen, p & Levin, B, editors]. London: WB Saunders Co. Ltd.Google Scholar
Reddy, BS & Maruyama, H (1986) Effect of dietary fish oil on azoxymethane-induced colon carcinogenesis in male F344 rats. Cancer Research 46, 33673370.Google ScholarPubMed
Roitt, IM, Brostoff, J & Male, DK (1993) Immunology, 3rd ed, London: Mosby.Google Scholar
Rüschoff, J, Wallinger, S, Dietmaier, W, Bocker, T, Brockhoff, G, Hofstädter, F & Fishel, R (1998) Aspirin suppresses the mutator phenotype associated with hereditary nonpolyposis colorectal cancer by genetic selection. Proceedings of the National Academy of Sciences USA 95, 1130111306.CrossRefGoogle ScholarPubMed
Schwartz, B, Avivi-Green, C & Polak-Charcon, S (1998) Sodium butyrate induces retinoblastoma protein phosphorylation, p16 expression and growth arrest of colon cancer cells. Molecular and Cellular Biochemistry 188, 2130.Google Scholar
Shoemaker, AR, Gould, KA, Luongo, C, Moser, AR & Dove, WF (1997) Studies of neoplasia in the Min mouse. Biochemica et Biophysica Acta 1332, F25-F48.Google Scholar
Stewart, T, Henderson, R, Grayson, H & Opelz, G (1997) Reduced incidence of rectal cancer, compared to gastric and colonic cancer, in a population of 73,076 men and women chronically immunosuppressed. Clinical Cancer Research 3, 5155.Google Scholar
Su, LK, Kinzler, KW, Vogelstein, B, Preisinger, AC, Moser, AR, Luongo, C, Gould, KA & Dove, WF (1992) Multiple intestinal neoplasia caused by a mutation in the murine homologue of the APC gene. Science 256, 668670.CrossRefGoogle Scholar
Vallance, C, Coaker, J & Mathers, JC (1999) Guar gum increases but cholesterol suppresses intestinal tumorigenesis in the Min mouse. Proceedings of the Nutrition Society 58, 72A.Google Scholar
Walter, DJ, Eastwood, MA, Brydon, WG & Elton, RA (1986) An experimental design to study colonic fibre fermentation in the rat: the duration of feeding. British Journal of Nutrition 55, 456479.Google Scholar
Wasan, HS, Novelli, M, Bee, J & Bodmer, WF (1997) Dietary fat influences polyp phenotype in multiple intestinal neoplasia mice. Proceedings of the National Academy of Sciences USA 94, 33083313.Google Scholar
Webb, SJ, Nicholson, D, Bubb, VJ & Wyllie, AH (1999) Caspase-mediated cleavage of APC results in an amino terminal fragment with an intact armadillo repeat domain. FASEB Journal 13, 339346.CrossRefGoogle Scholar
Wielenga, VJM, Smits, R, Korinek, V, Smit, L, Kielman, M, Fodde, R, Clevers, H & Pals, ST (1999) Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. American Journal of Pathology 154, 515523.Google Scholar
Williamson, SLH, Kartheuser, A, Coaker, J, Dehghan, Kooshkghazi M, Fodde, R, Burn, J & Mathers, JC (1999) Intestinal tumorigenesis in the Apc1638N mouse treated with aspirin and resistant starch for up to 5 months. Carcinogenesis 20, 805810.Google Scholar
Young, GP, McIntyre, A, Albert, V, Folino, M, Muir, JG & Gibson, PR (1996) Wheat bran suppresses potato starch-potentiated colorectal tumorigenesis at the aberrant crypt stage in a rat model. Gastroenterology 110, 508514.CrossRefGoogle ScholarPubMed
Zeytun, A, Hassuneh, M, Nagarkatti, M & Nagaratti, PS (1997) Fas-Fas ligand-based interactions between tumor cells and tumor-specific cytotoxic T lymphocytes: A lethal two-way street. Blood 90, 19521959.Google Scholar
Zoran, DL, Turner, ND, Taddeo, SS, Chapkin, RS & Lupton, JR (1997) Wheat bran reduces tumor incidence in a rat model of colon cancer independent of effects on distal luminal butyrate concentrations. Journal of Nutrition 127, 22172225.CrossRefGoogle Scholar