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Diets enriched with cereal brans or inulin modulate protein kinase C activity and isozyme expression in rat colonic mucosa

Published online by Cambridge University Press:  09 March 2007

Anne-Maria Pajari*
Department of Applied Chemistry and Microbiology, Nutrition, PO Box 27, 00014 University of Helsinki, Finland
Seija Oikarinen
Department of Applied Chemistry and Microbiology, Nutrition, PO Box 27, 00014 University of Helsinki, Finland
Soile Gråsten
Department of Clinical Nutrition, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland
Marja Mutanen
Department of Applied Chemistry and Microbiology, Nutrition, PO Box 27, 00014 University of Helsinki, Finland
*Corresponding author: Anne-Maria Pajari, fax +358 9 19158269, email
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The role of dietary fibres in colon carcinogenesis is controversial. To elucidate the mechanisms by which different dietary fibre sources may affect colonic tumour development, we studied the effects of diets enriched with cereal brans or inulin on protein kinase C (PKC) activity and isozyme expression in rat colon. Male Wistar rats (twelve per group) were fed one of the following AIN-93G-based diets () for 4 weeks: a non-fibre high-fat diet or one of the four high-fat diets supplemented with either rye, oat or wheat bran or inulin at 100 g/kg diet. The fat concentration (20 g/100 g) and fatty acid composition of the non-fibre high-fat diet was designed to approximate that in a typical Western-type diet. In the proximal colon, rats fed the inulin diet had a significantly higher membrane PKC activity and a higher membrane PKC δ level than rats fed the non-fibre diet (P<0·05). In the distal colon, rats fed the inulin and oat bran diets had a higher total PKC activity and a higher membrane PKC β2 level than rats fed the wheat-bran diet. Rats in the non-fibre and wheat-bran groups had the lowest concentrations of luminal diacylglycerol. In conclusion, feeding of wheat bran resulted in low distal PKC activity and expression of PKC β2, a PKC isozyme related to colonic cell proliferation and increased susceptibility for colon carcinogenesis, which may explain in part the protective effect of wheat bran against tumour development in a number of experimental colon cancer studies. The increase in PKC activity and PKC β2 expression by feeding inulin may be a drawback of inulin as a functional food.

Research Article
Copyright © The Nutrition Society 2000


Adlercreutz, H and Mazur, W (1997) Phyto-oestrogens and Western diseases. Annals of Medicine 29, 95120.Google Scholar
Baum, CL, Wali, RK, Sitrin, MD, Bolt, MJG and Brasitus, TA (1990) 1,2-Dimethylhydrazine-induced alterations in protein kinase C activity in the rat preneoplastic colon. Cancer Research 50, 39153920.Google Scholar
Berra, E, Diaz-Meco, MT, Dominguez, I, Municio, MM, Sanz, L, Lozano, J, Chapkin, RS and Moscat, J (1993) Protein kinase C ζ isoform is critical for mitogenic signal transduction. Cell 74, 555563.Google Scholar
Bufill, JA (1990) Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Annals of International Medicine 113, 779788.Google Scholar
Craven, PA and DeRubertis, FR (1992) Alterations in protein kinase C in 1,2-dimethylhydrazine induced colonic carcinogenesis. Cancer Research 52, 22162221.Google Scholar
Davidson, LA, Jiang, Y-H, Derr, JN, Aukema, HM, Lupton, JR and Chapkin, RS (1994) Protein kinase C isoforms in human and rat colonic mucosa. Archives in Biochemistry and Biophysics 312, 547553.Google Scholar
Davies, MJ, Bowey, EA, Adlercreutz, H, Rowland, IR and Rumsby, PC (1999) Effects of soy or rye supplementation of high-fat diets on colon tumour development in azoxymethane-treated rats. Carcinogenesis 20, 927931.Google Scholar
Dominguez, I, Diaz-Meco, MT, Municio, MM, Berra, E, de Garcia, HA, Cornet, ME, Sanz, L and Moscat, J (1992) Evidence for a role of protein kinase C ζ subspecies in maturation of. Xenopus laevis oocytes. Molecular and Cellular Biology 12, 37763783.Google Scholar
Frey, MR, Saxon, ML, Zhao, X, Rollins, A, Evans, SS and Black, JD (1997) Protein kinase C isozyme-mediated cell cycle arrest involves induction of p21(waf1/cip1) and p27(kip1) and hypophosphorylation of the retinoblastoma protein in intestinal epithelial cells. Journal of Biological Chemistry 272, 94249435.Google Scholar
Gibson, GR and Roberfroid, MB (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. Journal of Nutrition 125, 14011412.Google Scholar
Guillem, JG, O′Brian, CA, Fitzer, CJ, Forde, KA, LoGerfo, P, Treat, M and Weinstein, IB (1987) Altered levels of protein kinase C and Ca2+-dependent protein kinases in human colon carcinomas. Cancer Research 47, 20362039.Google Scholar
Jacobs, LR and Lupton, JR (1986) Relationship between colonic luminal pH, cell proliferation and colon carcinogenesis in 1,2-dimethylhydrazine treated rats fed high fibre diets. Cancer Research 46, 17271734.Google Scholar
Jacobs, DR, Marquart, L, Slavin, J and Kushi, LH (1998) Whole-grain intake and cancer: an expanded review and meta analysis. Nutrition and Cancer 30, 8596.Google Scholar
Jacobs, DR, Slavin, J and Marquart, L (1995) Whole-grain intake and cancer: a review of the literature. Nutrition and Cancer 24, 221229.Google Scholar
Jenab, M and Thompson, LU (1998) The influence of phytic acid in wheat bran on early biomarkers of colon carcinogenesis. Carcinogenesis 19, 10871092.Google Scholar
Jiang, Y-H, Lupton, JR and Chapkin, RS (1997) Dietary fat and fibre modulate the effect of carcinogen on colonic protein kinase C ƛ expression in rats. Journal of Nutrition 127, 19381943.Google Scholar
Jiang, Y-H, Lupton, JR and Chapkin, RS (1997) Dietary fish oil blocks carcinogen-induced down-regulation of colonic protein kinase C isozymes. Carcinogenesis 18, 351357.Google Scholar
Kahl-Rainer, P, Karner-Hanusch, J, Weiss, W and Marian, B (1994) Five of six protein kinase C isoenzymes present in normal mucosa show reduced protein levels during tumor developement in the human colon. Carcinogenesis 15, 779782.Google Scholar
Kusunoki, M, Sakannoue, Y, Hatada, T, Yanagi, H, Yamamura, T and Utsunomiya, J (1992) Correlation between protein kinase C activity and histopathological criteria in human colorectal adenoma. British Journal of Cancer 65, 673676.Google Scholar
Laemmli, UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680685.Google Scholar
Levy, MF, Pocsidio, J, Guillem, JG, Forde, K, LoGerfo P and Weinstein, IB (1993) Decreased levels of protein kinase C enzyme activity and protein kinase C mRNA in primary colon tumors. Diseases of the Colon and Rectum 36, 913921.Google Scholar
Liu, Q, Ning, W, Dantzer, R, Freund, GG and Kelley, KW (1998) Activation of protein kinase C-ζ and phosphatidylinositol 3′-kinase and promotion of macrophage differentiation by insulin-like growth factor-I. Journal of Immunology 160, 13931401.Google Scholar
McIntry, A, Gibson, PR and Yong, GP (1993) Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut 34, 386391.Google Scholar
Morotomi, M, Guillem, JG, LoGerfo P and Weinstein, IB (1990) Production of diacylglycerol, an activator of protein kinase C, by human intestinal microflora. Cancer Research 50, 35953599.Google Scholar
Morotomi, M, LoGerfo, P and Weinstein, IB (1991) Fecal excretion, uptake and metabolism by colon mucosa of diacylglycerol in rats. Biochemical and Biophysical Research Communications 181, 10281034.Google Scholar
Murray, NR, Davidson, LA, Chapkin, RS, Gustafson, WC, Schattenberg, DG and Fields, AP (1999) Overexpression of protein kinase C βII induces colonic hyperproliferation and increased sensitivity to colon carcinogenesis. Journal of Cell Biology 145, 699711.Google Scholar
Mutanen, M, Pajari, A-M and Oikarinen, SI (2000) Beef induces and rye bran prevents formation of intestinal polyps in APCMin mice – relation to β-catenin and PKC isozymes. Carcinogenesis 21, 11671173.Google Scholar
Nishizuka, Y (1995) Protein kinase C and lipid signaling for sustained cellular responses. FASEB Journal 9, 484496.Google Scholar
Pajari, A-M, Häkkänen, P, Duan, R-D and Mutanen, M (1998) Role of red meat and arachidonic acid in protein kinase C activation in rat colonic mucosa. Nutrition and Cancer 32, 8694.Google Scholar
Perletti, GP, Marras, E, Concari, P, Piccini, F and Tashjian, AH (1999) PKCdelta acts as a growth and tumor suppressor in rat colonic epithelial cells. Oncogene 18, 12511256.Google Scholar
Pickering, JS, Lupton, JR and Chapkin, RS (1995) Dietary fat, fiber, and carcinogen alter fecal diacylglycerol composition and mass. Cancer Research 55, 22932298.Google Scholar
Pongracz, J, Clark, P, Neoptolemos, JP and Lord, JM (1995) Expression of protein kinase C isoenzymes in colorectal cancer tissue and their differential activation by different bile acids. International Journal of Cancer 61, 3539.Google Scholar
Reddy, BS, Simi, B and Engle, A (1994) Biochemical epidemiology of colon cancer: effect of types of dietary fiber on colonic diacylglycerols in women. Gastroenterology 106, 883889.Google Scholar
Reddy, BS, Hamid, R and Rao, CV (1997) Effect of dietary oligofructose and inulin on colonic preneoplastic aberrant crypt foci inhibition. Carcinogenesis 18, 13711374.Google Scholar
Reeves, PG, Nielsen, FH and Fahey, GC (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Committee on the reformulation of the AIN-76A rodent diet. Journal of Nutrition 123, 19391951.Google Scholar
Rowland, IR, Rumney, CJ, Coutts, JT and Lievense, LC (1998) Effect of. Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced aberrant crypt foci in rats. Carcinogenesis 19, 281285.Google Scholar
Sauma, S and Friedman, E (1996) Increased expression of protein kinase C beta activates ERK3. Journal of Biological Chemistry 271, 11221142.Google Scholar
Sauma, S, Yan, Z, Ohno, S and Friedman, E (1996) Protein kinase C beta 1 and protein kinase C beta 2 activate p57 mitogen-activated protein kinase and block differentiation in colon carcinoma cells. Cell Growth and Differentiation 7, 587594.Google Scholar
Scaglione-Sewell, BA, Abraham, C, Bissonnette, M, Skarosi, SF, Hart, J, Davidson, NO, Wali, RK, Sitrin, M and Brasitus, TA (1998) Decreased PKC-alpha expression increases cellular proliferation, decreases differentiation, and enhances the transformed phenotype of CaCo-2 cells. Cancer Research 58, 10741081.Google Scholar
Sheng, S and Schuster, SM (1992) Simple modifications of a protein immunoblotting protocol to reduce nonspecific background. BioTechniques 13, 704708.Google Scholar
Towbin, H, Staehelin, T and Gordon, J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proceedings of the National Academy of Sciences USA 76, 43504354.Google Scholar
Wali, RK, Baum, CL, Bolt, MJG, Dudeja, PK, Sitrin, MD and Brasitus, TA (1991) Down-regulation of protein kinase C activity in 1,2-dimethylhydrazine-induced rat colonic tumors. Biochimica et Biophysica Acta 1092, 119123.Google Scholar
Wali, RK, Frawley, BP, Hartmann, S, Roy, HK, Khare, S, Scaglione-Sewell, B, Earnest, DL, Sitrin, MD, Brasitus, TA and 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 Research 55, 52575264.Google Scholar
Zoran, DL, Turner, ND, Taddeo, SS, Chapkin, RS and Lupton, JR (1997) Wheat bran diet reduces tumor incidence in a rat model of colon cancer independent of effects on distal luminal butyrate concentrations. Journal of Nutrition 127, 22172225.Google Scholar