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Mixtures of SCFA, composed according to physiologically available concentrations in the gut lumen, modulate histone acetylation in human HT29 colon cancer cells

Published online by Cambridge University Press:  08 March 2007

Jeannette Kiefer ,
Gabriele Beyer-Sehlmeyer  and
Beatrice L. Pool-Zobel
Jeannette Kiefer
Affiliation:
Department of Nutritional Toxicology, Institute for Nutrition, Friedrich-Schiller-University, Dornburger Str. 25, D-07743 Jena, Germany
Gabriele Beyer-Sehlmeyer
Affiliation:
Department of Nutritional Toxicology, Institute for Nutrition, Friedrich-Schiller-University, Dornburger Str. 25, D-07743 Jena, Germany
Beatrice L. Pool-Zobel*
Affiliation:
Department of Nutritional Toxicology, Institute for Nutrition, Friedrich-Schiller-University, Dornburger Str. 25, D-07743 Jena, Germany
*
*Corresponding author: Professor Beatrice L. Pool-Zobel, fax +49 3641 949672, email b8pobe@uni-jena.de
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Abstract

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Intake of fibre has beneficial properties on gut health. Butyrate, a product of bacterial gut fermentation, is thought to contribute to positive effects by retarding growth and enhancing apoptosis of tumour cells. One mechanism is seen in its capacity to modulate histone acetylation and thereby transcriptional activity of genes. Next to butyrate, propionate and acetate are also major products of gut fermentation and together they may exert different potencies of cellular effects than butyrate alone. Since virtually nothing is known on combination effects by SCFA mixtures, here we had the aim to assess how physiological relevant concentrations and mixtures of SCFA modulate histone acetylation in human colon cells. HT29 colon cancer cells were incubated with mixtures of butyrate, acetate and propionate and with the individual compounds as controls. Histone acetylation was determined with acid-urea gel electrophoresis and immunoblotting. Acetylated histones slowly increased over 24 h and persisted up to 72 h in butyrate-treated HT29 cells. Butyrate (5–40 mm) and propionate (20–40 mm) enhanced histone acetylation significantly after 24 h incubation, whereas acetate (2·5–80 mm) was ineffective. Mixtures of these SCFA also modulated histone acetylation, mainly due to additive effects of butyrate and propionate, but not due to acetate. In conclusion, physiological concentrations of propionate together with butyrate could have more profound biological activities than generally assumed. Together, these SCFA could possibly mediate important processes related to an altered transcriptional gene activation and thus contribute to biological effects possibly related to cancer progression or prevention.

Keywords

SCFAHistone acetylationColon tumour cells
Type
Research Article
Information
British Journal of Nutrition , Volume 96 , Issue 5 , November 2006 , pp. 803 - 810
Copyright
Copyright © The Nutrition Society 2006

References

Abrahamse, SL, Pool-Zobel, BL & Rechkemmer, G (1999) Potential of short chain fatty acids to modulate the induction of DNA damage and changes in the intracellular calcium concentration in isolated rat colon cells. Carcinogenesis 20, 629–634.CrossRefGoogle Scholar
Ajiro, K, Borun, TW & Cohen, LH (1981) Phosphorylation states of different histone 1 subtypes and their relationship to chromatin functions during the HeLa S-3 cell cycle. Biochemistry 20, 1445–1454.CrossRefGoogle ScholarPubMed
Alles, MS, Hartemink, R, Meyboom, S, Harryvan, JL, Van Laere, KMJ, Nagengast, FM & Hautvast, JGAJ (1999) Effect of transgalactooligosaccharides on the composition of the human intestinal microflora and putative risk markers for colon cancer. Am J Clin Nutr 69, 980–991.CrossRefGoogle ScholarPubMed
Archer, SY, Meng, S, Shei, A & Hodin, RA (1998) p21WAF1 is required for butyrate-mediated growth inhibition of human colon cancer cells. Cell Biol 95, 6791–6796.Google ScholarPubMed
Barnard, JA & Warwick, G (1993) Butyrate rapidly induces growth inhibition and differentiation in HT-29 cells. Cell Growth Differ 4, 495–501.Google ScholarPubMed
Barry, J-L, Hoebler, C, Macfarlane, G, Macfarlane, S, Mathers, J, Reed, K, Mortensen, P, Nordgaard, I, Rowland, I & Rumney, C (1995) Estimation of the fermentability of dietary fibre in vitro: a European interlaboratory study. Br J Nutr 74, 303–322.CrossRefGoogle ScholarPubMed
Beyer-Sehlmeyer, G, Glei, M, Hartmann, E, Hughes, R, Persin, CBöhm, V, Rowland, I, Schubert, R, Jahreis, G & Pool-Zobel, BL (2003) Butyrate is only one of several growth inhibitors produced during gut flora-mediated fermentation of dietary fibre sources. Br J Nutr 90, 1–15.CrossRefGoogle ScholarPubMed
Bingham, SA, Norat, T & Moskal, A (2005) Is the association with fiber from foods in colorectal cancer confounded by folate intake? Cancer Epidemiol Biomarkers Prev 14, 1552–1556.CrossRefGoogle ScholarPubMed
Bradford, MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248–254.CrossRefGoogle ScholarPubMed
Chen, WY & Townes, TM (2000) Molecular mechanism for silencing virally transducted genes involves histone deacetylation and chromatin condensation. Proc Natl Acad Sci USA 97, 377–382.CrossRefGoogle ScholarPubMed
Cousens, LS, Gallwitz, D & Alberts, BM (1979) Different accessibilities in chromatin to histone acetylase. J Biol Chem 254, 1716–1723.CrossRefGoogle ScholarPubMed
Ebert, MN, Beyer-Sehlmeyer, G, Liegiebel, UM, Kautenburger, T, Becker, TW & Pool-Zobel, BL (2001) Butyrate induces glutathione S-transferases in human colon cells and protects from genetic damage by 4-hydroxy-2-nonenal. Nutr Cancer 41, 156–164.CrossRefGoogle Scholar
Ebert, MN, Klinder, A, Peters, WH, Schaferhenrich, A, Sendt, W, Scheele, J & Pool-Zobel, BL (2003) Expression of glutathione S-transferases (GSTs) in human colon cells and inducibility of GSTM2 by butyrate. Carcinogenesis 24, 1637–1644.CrossRefGoogle ScholarPubMed
Fogh, J & Trempe, X (1975) Human tumor cells in vitro. In Human Tumor Cells In Vitro, pp. 115–159 [Fogh, J, editor]. New York: Plenum Press.CrossRefGoogle Scholar
Gaudier, E, Jarry, A, Blottière, HM, de Coppet, P, Buisine, MP, Aubert, JP, Laboisse, C, Cherbut, C & Hoebler, C (2004) Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose. Am J Physiol Gastrointest Liver Physiol 287, G1168–G1174.CrossRefGoogle ScholarPubMed
Hague, A & Paraskeva, C (1995) The short-chain fatty acid butyrate induces apoptosis in colorectal tumour cell lines. Eur J Cancer Prev 4, 359–364.CrossRefGoogle ScholarPubMed
Heavey, PM, McKenna, D & Rowland, IR (2004) Colorectal cancer and the relationship between genes and the environment. Nutr Cancer 48, 124–141.CrossRefGoogle ScholarPubMed
Hinnebusch, BF, Meng, S, Wu, JT, Archer, SY & Hodin, RA (2002) The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation. J Nutr 132, 1012–1017.CrossRefGoogle ScholarPubMed
Iacomino, G, Tecce, MF, Grimaldi, C, Tosto, M & Russo, GL (2001) Transcriptional response of a human colon adenocarcinoma cell line to sodium butyrate. Biochem Biophys Res Commun 285, 1280–1289.CrossRefGoogle ScholarPubMed
Jenkins, DJA, Kendall, CWC & Vuksan, V (1999) The effect of wheat bran particle size on laxation and colonic fermentation. J Am Coll Nutr 18, 339–345.CrossRefGoogle ScholarPubMed
Johnson, IT (1995) Butyrate and markers of neoplastic change in the colon. Eur J Cancer Prev 4, 365–371.CrossRefGoogle ScholarPubMed
Kautenburger, T, Beyer-Sehlmeyer, G & Festag, G (2005) The gut fermentation product butyrate, a chemopreventive agent, suppresses glutathione S-transferase theta (hGSTT1) and cell growth more in human colon adenoma (LT97) than tumor (HT29) cells. J Cancer Res Clin Oncol 131, 692–700.CrossRefGoogle ScholarPubMed
Klampfer, L, Huang, J, Sasazuki, T, Shirasawa, S & Augenlicht, L (2003) Inhibition of interferon gamma signalling by the short chain fatty acid butyrate. Mol Canc Res 1, 855–862.Google ScholarPubMed
Knudsen, BKE, Johansen, HN & Glitso, V (1997) Rye dietary fiber and fermentation in the colon. Am Ass Cer Chem 42, 690–694.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, 386–391.CrossRefGoogle ScholarPubMed
Marks, PA, Rifkind, RA, Richon, VM, Breslow, R, Miller, T & Kelly, WK (2001) Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer 1, 194–202.CrossRefGoogle ScholarPubMed
O'Neil, LP, Keohane, AM, Lavender, JS, McCrabe, V, Heard, E, Avner, P, Brockdorff, N & Turner, BM (1999) A developmental switch in H4 acetylation upstream of Xist plays a role in X chromosome inactivation. EMBO J 18, 2897–2907.CrossRefGoogle Scholar
Pender, SLF, Quinn, JJ, Sanderson, IR & MacDonald, T (2000) Butyrate upregulates stromelysin-1 production by intestinal mesenchymal cells. Am J Physiol Gastrointest Liver Physiol 279, G918–G924.CrossRefGoogle ScholarPubMed
Peters, U, Sinha, R & Chatterjee, N (2003) Dietary fibre and colorectal adenoma in a colorectal cancer early detection programme. Lancet 361, 1491–1495.CrossRefGoogle Scholar
Pool-Zobel, BL, Veeriah, R, Sauer, J, Kautenburger, T, Kiefer, J, Richter, KK, Soom, M & Wölfl, S (2005) Butyrate may enhance toxicological defence in primary, adenoma and tumor human colon cells by favourably modulating expression of glutathione S-transferases genes, an approach in nutrigenomics. Carcinogenesis 26, 1064–1076.CrossRefGoogle ScholarPubMed
Ragione, FD, Criniti, V, Della Pietra, VBorriello, A, Oliva, A, Indaco, S, Yamamoto, T & Zappia, V (2001) Genes modulated by histone acetylation as new effectors of butyrate activity. FEBS Lett 499, 199–204.CrossRefGoogle ScholarPubMed
Roberfroid, MB (2005) Inulin-Type Fructans. Functional Food Ingredients. Boca Raton, Florida: CRC Press.Google Scholar
Sambucetti, LC, Fischer, DD, Zabludoff, S, Kwon, PO, Chamberlin, H, Trogani, N, Xu, H & Cohen, D (1999) Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects. J Biol Chem 274, 34940–34947.CrossRefGoogle ScholarPubMed
Scheppach, W (1994) Effects of short chain fatty acids on gut morphology and function. Gut 35, S35–S38.CrossRefGoogle ScholarPubMed
Schröder, O & Stein, J (1997) Kurzkettige fettsäuren - physiologie und pathophysiologische implikationen (Short chain fatty acids - physiology and pathophysiologic implications). Akt Ernähr -Med 22, 86–96.Google Scholar
Siavoshian, S, Segain, J-P, Kornprobst, M, Cherbut, C, Galmiche, J-P & Blottière, HM (2000) Butyrate and trichostatin A effects on the proliferation/differentiation of human intestinal cells: induction of cyclin D3 and p21 expression. Gut 46, 507–514.CrossRefGoogle ScholarPubMed
Topping, DL & Clifton, PM (2001) Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev 81, 1031–1064.CrossRefGoogle ScholarPubMed
Wächterhäuser, A & Stein, J (2000) Rationale for the luminal provision of butyrate in intestinal deaseases. Eur J Nutr 39, 164–171.Google Scholar
Wattenberg, LW (1992) Inhibition of carcinogenesis by minor dietary constituents. Cancer Res 52, 2085s–2091s.Google ScholarPubMed
Wu, JT, Archer, SY, Hinnebusch, B, Meng, S & Hodin, RA (2001) Transient vs. prolonged histone hyperacetylation: effects on colon cancer cell growth, differentiation, and apoptosis. Am J Physiol Gastrointest Liver Physiol 280, 482–490.CrossRefGoogle ScholarPubMed