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Butyrate-Induced Cell Death and Differentiation Are Associated with Distinct Patterns of ROS in HT29-Derived Human Colon Cancer Cells

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Abstract

To investigate the role of reactive oxygen species (ROS) induced by butyrate in tumor cells, we compared HT29R, an HT29-derived human colon cancer cell line refractory to butyrate-induced cell differentiation but highly sensitive to cell death, with the differentiation-positive HT29-12 and HT29-21 cell lines (exhibiting low sensitivity to butyrate-induced cell death), with respect to levels of butyrate-induced free radicals (FRs), ROS, and H2O2. Dose-dependent increase of FRs (as determined by electron spin resonance spectroscopy) and ROS (dichlorofluorescein assay) was induced in HT29R, but not in HT29-12 and HT29-21 cells, where, in contrast to HT29R, a dose-dependent increase of H2O2 release (phenol red assay) was induced by butyrate. The mode of butyrate-induced cell death in HT29R cells was of a mixed type with necrosis predominating, which, however, switched to apoptosis as the major type of cell death in the presence of the drugs 1,5-dihydroxyisoquinoline, resveratrol, or cyclosporine A. The results suggest that FRs and ROS induced by butyrate in HT29R cells are products of cell death, while H2O2 induced in HT29-12 and HT29-21 cells is functionally related to cell differentiation.

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Acknowledgments

This research was supported by grants of the Hungarian Research Fund OTKA K 76133, OTKA T 49753, and the Österreichische Forschungsgemeinschaft (Project MOEL 339). We are indebted to Ms. Rajam Csordas-Iyer for critical reading and linguistic corrections.

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Authors and Affiliations

  1. Institute of Physiology and Biochemistry, Faculty of Veterinary Sciences, Szent Istvan University, Istvan u. 2, 1078, Budapest, Hungary

    Monika Domokos & Zsuzsanna Neogrady

  2. Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeri ut 59-67, 1025, Budapest, Hungary

    Judit Jakus

  3. Institute of Pharmacology and Toxicology, Faculty of Veterinary Sciences, Szent Istvan University, Istvan u. 2, 1078, Budapest, Hungary

    Krisztina Szeker, Rita Csizinszky, György Csiko & Peter Galfi

  4. Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Fritz-Pregl-Str. 3, 6020, Innsbruck, Austria

    Adam Csordas

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  1. Monika Domokos
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Correspondence to Adam Csordas.

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Domokos, M., Jakus, J., Szeker, K. et al. Butyrate-Induced Cell Death and Differentiation Are Associated with Distinct Patterns of ROS in HT29-Derived Human Colon Cancer Cells. Dig Dis Sci 55, 920–930 (2010). https://doi.org/10.1007/s10620-009-0820-6

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  • DOI: https://doi.org/10.1007/s10620-009-0820-6

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