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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

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Abstract

Purpose: The gut fermentation product of dietary fiber, butyrate, inhibits growth of HT29, an established tumor cell line. It also induces detoxifying enzymes belonging to the glutathione S-transferase family (GSTs), namely hGSTM2, hGSTP1, hGSTA4, but not of hGSTT1 . Here we investigated kinetics of effects in HT29 and compared sensitivities with preneoplastic LT97 colon adenoma cells, to assess mechanisms of colon cancer chemoprevention in two stages of cell transformation. Methods: We determined cell growth after butyrate treatment by quantifying DNA, GST expression by Northern/Western Blotting or biochemical analysis and butyrate consumption by measuring the residual concentrations in the cell culture supernatants. Stability of GST-theta (hGSTT1) mRNA was assessed in HT29 cells after inhibition of transcription with actinomycin D. Results: LT97 adenoma cells consumed twofold more butyrate and were more sensitive to growth inhibition than HT29 (EC501.9 mM and 4.0 mM, respectively). Butyrate did not induce GSTs, but instead reduced hGSTT1 in LT97 and HT29. Conclusions: Butyrate has suppressing-agent activities in human colon cells by inhibiting two survival factors, namely hGSTT1 and cell growth, with LT97 more sensitive than HT29. These findings indicate that butyrate formation in the gut lumen of humans could be protective by reducing survival of transformed colon cells.

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Acknowledgements

We gratefully acknowledge the excellent technical assistance by Ms. Esther Hartmann and Ms. Nadine Knoll. We thank Professor Dr. Gerhard Jahreis and Peter Möckel of the Department of Physiology of Nutrition in Jena for analyzing the short chain fatty acids in the cell culture supernatants. We are grateful to Dr. Rosalie Elespuru for valuable discussion and editorial comments. Parts of this work have been carried out with financial support of the Deutsche Krebshilfe (10-1572-Po-1), the Bundesministerium für Ernährung, Landwirtschaft und Forsten (99-HS-039) and the Deutsche Forschungsgemeinschaft (PO 284/8-1).

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Authors and Affiliations

  1. Department of Nutritional Toxicology, Institute for Nutrition, Friedrich-Schiller-University, Dornburger Str. 25, 07743, Jena, Germany

    Tanja Kautenburger, Gabriele Beyer-Sehlmeyer, Grit Festag, Natja Haag, Stephanie Kühler & Beatrice L. Pool-Zobel

  2. Institut für Humangenetik und Anthropologie, Klinikum der Friedrich-Schiller-Universität Jena, Kollegiengasse 10, 07740, Jena, Germany

    Alma Küchler, Anja Weise, Thomas Liehr & Uwe Claussen

  3. Institute of Cancer Research, University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria

    Brigitte Marian

  4. Department of Gastroenterology, St Radboud University Hospital, Nijmegen, The Netherlands

    Wilbert H. M. Peters

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  1. Tanja Kautenburger
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  2. Gabriele Beyer-Sehlmeyer
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  12. Beatrice L. Pool-Zobel
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Correspondence to Beatrice L. Pool-Zobel.

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Kautenburger, T., Beyer-Sehlmeyer, G., Festag, G. et al. 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 (2005). https://doi.org/10.1007/s00432-005-0013-4

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