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Effects of a flaxseed mixture and plant oils rich in α-linolenic acid on the adenoma formation in multiple intestinal neoplasia (Min) mice

  • Seija I. Oikarinen (a1), Anne-Maria Pajari (a1), Irma Salminen (a2), Satu-Maarit Heinonen (a3), Herman Adlercreutz (a3) and Marja Mutanen (a1)...

Abstract

Flaxseed is a dietary source of possible chemopreventive compounds such as lignans and α-linolenic acid (ALA). To study the effects of a flaxseed mixture on adenoma formation in multiple intestinal neoplasia mice, the mice were fed a diet containing 2·7 % flaxseed, 4·5 % fibre and 3·7 % ALA. To elucidate the effect of oils of the mixture we also composed a diet without flaxseed but with the same oil composition. The median number of adenomas in the small intestine was fifty-four for the control group, and thirty-seven (P=0·023) and forty-two (P=0·095) for flaxseed and oil groups, respectively. Compared with controls (1·2 mm), the adenoma size was smaller in the flaxseed (0·9 mm; P=0·002) and oil (1·0 mm; P=0·012) groups. Both diets changed the proportions of n-3 and n-6 fatty acids in the colonic mucosa. Membrane β-catenin and protein kinase C (PKC)-ζ levels were reduced in the adenoma v. mucosa (P<0·05), and an inverse association was found between the membrane PKC-ζ in the mucosa and the adenoma number (r −0·460, P=0·008, n 32). Only the flaxseed diet increased lignan levels in the caecum (P=0·002) and in plasma (P=0·002) but they were not associated with tumour formation. The results suggest that the preventive effect of flaxseed on colon carcinogenesis may be due to the oil part of flaxseed, and the loss of β-catenin and PKC-ζ from the membranes of the mucosal tissue may play a permissive role in intestinal tumour development.

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Corresponding author

*Corresponding author: Dr Seija I. Oikarinen, fax +358 9 191 58 269, email seija.oikarinen@helsinki.fi

References

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Adlercreutz, H (1998) Human health and phytoestrogen. In Reproductive and Developmental Toxicology, pp. 299371 [Korach, KS, editor]. New York: Marcel Dekker Inc.
Adlercreutz, H (2002) Phyto-oestrogens and cancer. Lancet Oncol 3, 364373.
Adlercreutz, H, Wang, GJ, Lapcík, O, Hampl, R, Wähälä, K, Mäkelä, T, Lusa, K, Talme, M & Mikola, H (1998) Time-resolved fluoroimmunoassay for plasma enterolactone. Anal Biochem 265, 208215.
Banan, A, Fields, JZ, Talmage, DA, Zhang, L & Keshavarzian, A (2002) PKC-ζ is required in EGF protection of microtubules and intestinal barrier integrity against oxidant injury. Am J Physiol 282, G794G808.
Black, JD (2001) Protein kinase C isozymes in colon carcinogenesis: guilt by omission. Gastroenterology 120, 18681872.
Corpet, DE & Pierre, F (2003) Point: from animal models to prevention of colon cancer. Systematic review of chemoprevention in Min mice and choice of model system. Cancer Epidemiol Biomark Prev 12, 391400.
Cowin, P (1994) Unravelling the cytoplasmic interactions of the cadherin superfamily. PNAS U S A 91, 1075910761.
Dabrosin, C, Chen, J, Wang, L & Thompson, LU (2002) Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts. Cancer Lett 185, 3137.
Davies, CD & Johnson, WT (2002) Dietary copper affects azoxymethane-induced intestinal tumor formation and protein kinase C isozyme and mRNA expression in colon of rats. J Nutr 132, 10181025.
Etienne-Manneville, S & Hall, A (2003 a) Cell polarity: Par6, aPKC and cytoskeletal crosstalk. Curr Opin Cell Biol 15, 6772.
Etienne-Manneville, S & Hall, A (2003 b) Cdc42 regulates GSK-3 β and adenomatous polyposis coli to control cell polarity. Nature 421, 753756.
Fodde, R, Smits, R & Clevers, H (2001) APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer 1, 5567.
Hansen, Petrik MB, McEntee, MF, Johnson, BT, Obukowicz, MG & Whelan, J (2000) Highly unsaturated (n-3) fatty acids, but not α-linolenic, conjugated linoleic or γ-linolenic acids, reduce tumorigenesis in APC Min/+ mice. J Nutr 130, 24342443.
Hara, A & Radin, NS (1978) Lipid extraction of tissues with a low-toxicity solvent. Anal Biochem 90, 420426.
He, T-C, Sparks, AB, Rago, C, Hermeking, H, Zawel, L, da Costa, LT, Morin, PJ, Vogelstein, B & Kinzler, KW (1998) Identification of c-MYC as a target of the APC pathway. Science 281, 15091512.
Henderson, BR (2000) Nuclear-cytoplasmic shuttling of APC regulates β-catenin subcellular localization and turnover. Nature Cell Biol 2, 653660.
Hioki, K, Shivapurkar, N, Oshima, H, Alabaster, O, Oshima, M & Taketo, MM (1997) Suppression of intestinal polyp development by low-fat and high-fibre diet in APC716 knockout mice. Carcinogenesis 18, 18631865.
Jenab, M & Thompson, LU (1996) The influence of flaxseed and lignans on colon carcinogenesis and β-glucuronidase activity. Carcinogenesis 17, 13431348.
Jenab, M & Thompson, LU (1998) The influence of phytic acid in wheat bran on early biomarkers of colon carcinogenesis. Carcinogenesis 19, 10871092.
Kahl-Reiner, P, Karner-Hanusch, J, Weiss, W & Marian, B (1994) Five of six protein kinase C isoenzymes present in normal mucosa show reduced protein levels during tumour development in the human colon. Carcinogenesis 15, 770782.
Kitts, DD, Yuan, YV, Wijewickreme, AN & Thompson, LU (1999) Antioxidant activity of the flaxseed lignan secoisolariciresinol diglycoside and its mammalian lignan metabolites enterodiol and enterolactone. Mol Cell Biochem 202, 91100.
Klein, IK, Ritland, SR, Burgart, LJ, Ziesmer, SC, Roche, PC, Gendler, SJ & Karnes, WE (2000) Adenoma-specific alterations of protein kinase C isozyme expression in APC Min mice. Cancer Res 60, 20772080.
Li, D, Yee, JA, Thompson, LU & Yan, L (1999) Dietary supplementation with secoisolariciresinol diglycoside (SDG) reduces experimental metastasis of melanoma cells in mice. Cancer Lett 142, 9196.
McEntee, MF, Chiu, C-H & Whelan, J (1999) Relationship of β-catenin and Bcl-2 expression to sulindac-induced regression of intestinal tumors in Min mice. Carcinogenesis 20, 635640.
McIntry, A, Gibson, PR & Yong, GP (1993) Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut 34, 386391.
Mutanen, M, Pajari, A-M & Oikarinen, SI (2000) Beef induces and rye bran prevents the formation of intestinal polyps in APC Min mice: relation to β-catenin and PKC-isozymes. Carcinogenesis 21, 11671173.
Narisawa, T, Fukaura, Y, Yazawa, K, Ishikawa, C, Isoda, Y & Nishizawa, Y (1994) Colon cancer prevention with a small amount of dietary perilla oil high in alpha-linolenic acid in an animal model. Cancer 15, 20692075.
Nishisho, I, Nakamura, Y, Miyoshi, Y, Miki, Y, Ando, H, Horii, A, Koyama, K, Utsunomiya, J, Baba, S & Hedge, P (1991) Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253, 665669.
Oikarinen, S, Heinonen, S-M, Nurmi, T, Adlercreutz, H & Mutanen, M (2005) No effect on adenoma formation in Min mice after moderate amount of flaxseed. Eur J Nutr 44, 273280.
Oikarinen, SI, Pajari, A-M & Mutanen, M (2000) Chemopreventive activity of crude hydroxymatairesinol (HMR) extract in APCMin mice. Cancer Lett 161, 253258.
Onogi, N, Okuno, M, Komaki, C, Moriwaki, H, Kawamori, T, Tanaka, T, Mori, H & Muto, Y (1996) Suppressing effect of perilla oil on azoxymethane-induced foci of colonic aberrant crypts in rats. Carcinogenesis 17, 12911296.
Oshima, M, Dinchuk, JE, Kargman, SL, Oshima, H, Hancock, B, Kwong, E, Trzaskos, JM, Evans, JF & Taketo, MM (1996) Suppression of intestinal polyposis in APC Δ716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87, 803809.
Pajari, A-M, Oikarinen, SI, Duan, R-D & Mutanen, M (2000) A high beef diet alters protein kinase C isozyme expression in rat colonic mucosa. J Nutr Biochem 11, 474481.
Pajari, A-M, Rajakangas, J, Päivärinta, E, Kosma, V-M, Rafter, J & Mutanen, M (2003) Promotion of intestinal tumour formation by inulin is associated with an accumulation of cytosolic β-catenin in Min mice. Int J Cancer 106, 653660.
Rao, CV, Cooma, I, Rodriguez, JGR, Simi, B, El-Bayoumy, K & Reddy, BS (2000) Chemoprevention of familial adenomatous polyposis development in the APCmin mouse model by 1,4-phenylene bis(methylene)selenocyanate. Carcinogenesis 21, 617621.
Reeves, PG, Nielsen, FH & Fahey, GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123, 19391951.
Roy, HK, Bissonnette, M, Frawley, BP Jr, Wali, RK, Niedziela, SM, Earnest, D & Brasitus, TA (1995) Selective preservation of protein kinase C-ζ in the chemoprevention of azoxymethane-induced colonic tumors by piroxicam. FEBS Lett 366, 143145.
Saxon, ML, Zhao, X & Black, JD (1994) Activation of protein kinase C isozymes is associated with post-mitotic events in intestinal epithelial cells in situ. J Cell Biol 126, 747763.
Schmelz, EM, Roberts, PC, Kustin, EM, Lemonnier, LA, Sullards, MC, Dillehay, DL & Merrill, AH Jr (2001) Modulation of intracellular β-catenin localization and intestinal tumorigenesis in vivo and in vitro by sphingolipids. Cancer Res 61, 67236729.
Serraino, M & Thompson, LU (1992) Flaxseed supplementation and early markers of colon carcinogenesis. Cancer Lett 63, 159165.
Steinbach, G, Lynch, PM, Phillips, RKS et al. , (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 29, 19461952.
Stewart, BW & Kleihues, P (2003) World Cancer Report. Lyon, France: IACR Press.
Stoffel, W, Chu, F & Ahrens, EH Jr (1959) Analysis of long-chain fatty acids by gas liquid chromatography. Anal Chem 31, 307308.
Stumpf, K, Uehara, M, Nurmi, T & Adlercreutz, H (2000) Changes in the time-resolved fluoroimmunoassay of plasma enterolactone. Anal Biochem 284, 153157.
Su, L-K, 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 homolog of the APC gene. Science 256, 668670.
Tetsu, O & McCormick, F (1999) β-Catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398, 422426.
Thompson, LU (1998) Experimental studies on lignans and cancer. Baillières Clin Endocrinol Metab 12, 691705.
Thompson, LU, Rickard, SE, Orcheson, LJ & Seidl, MM (1996) Flaxseed and its lignan and oil components reduce mammary tumor growth at the late stage of carcinogenesis. Carcinogenesis 17, 13731376.
Van Kranen, HJ, Mortensen, A, Sørensen, IK, van den Berg-Wijnands, J, Beems, R, Nurmi, T, Adlercreutz, H & Van Kreijl, CF (2003) Lignan precursors from flaxseed or rye bran do not protect against the development of intestinal neoplasia in APCMin mice. Nutr Cancer 45, 203210.
Verstovsek, G, Byrd, A, Frey, MR, Petrelli, NJ & Black, JD (1998) Colonocyte differentiation is associated with increased expression and altered distribution of protein kinase C isozymes. Gastroenterology 115, 7585.
Wali, RK, Bissonette, M, Khare, S, Aquino, B, Niedziela, S, Sitrin, M & Brasitus, TA (1996) Protein kinase C isoforms in the chemopreventive effects of a novel vitamin D3 analogue in rat colonic tumorigenesis. Gastroenterology 111, 118126.
Wali, RK, Frawley, BP, Hartmann, S, Roy, HK, Khare, S, Scaglione-Sewell, BA, Earnest, DL, Sitrin, MD, Brasitus, TA & Bissonette, M (1995) Mechanism of action of chemoprotective ursodeoxycholate in the azoxymethane model of rat colonic carcinogenesis: potential roles of protein kinase C-α, βII and ζ. Cancer Res 55, 52575264.
Willet, WC (2002) Balancing life-style and genomics research for disease prevention. Science 296, 695698.
Williams, CS, Luongo, C, Radhika, A, Zhang, T, Lamps, LW, Nanney, LB, Beauchamp, D & DuBois, RN (1996) Elevated cyclooxygenase-2 levels in Min mouse adenomas. Gastroenterology 111, 11341140.
Yu, CF, Whiteley, L, Carryl, O & Basson, MD (2001) Differential dietary effects on colonic and small bowel neoplasia in C57BL/6J APC Min/+ mice. Dig Dis Sci 46, 13671380.
Zoran, DL, Turner, ND, Taddeo, SS, Chapkin, RS & Lupton, JR (1997) Wheat bran diet reduces tumor incidence in a rat model of colon cancer independent of effects on distal luminal butyrate concentrations. J Nutr 127, 22172225.

Keywords

Effects of a flaxseed mixture and plant oils rich in α-linolenic acid on the adenoma formation in multiple intestinal neoplasia (Min) mice

  • Seija I. Oikarinen (a1), Anne-Maria Pajari (a1), Irma Salminen (a2), Satu-Maarit Heinonen (a3), Herman Adlercreutz (a3) and Marja Mutanen (a1)...

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