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Decitabine-induced apoptosis is derived by Puma and Noxa induction in chronic myeloid leukemia cell line as well as in PBL and is potentiated by SAHA

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An Erratum to this article was published on 23 February 2012

Abstract

Restoration of cellular apoptotic pathways plays a crucial role in cancer therapy strategies. In a broad spectrum of anticancer drugs, epigenetic effectors are in the center of interest mostly because of potential reversibility of their action. Methylation status of the cells is influenced by methyltransferase inhibitor 2-deoxy-5′-azacytidine (decitabine, DAC), but higher concentrations of this agent cause a DNA-damage. In our study, tumor supressor p53-apoptotic pathway was activated in decitabine-induced cell death. Expression of p53-inducible BH3-only apoptotic proteins Puma and Noxa was elevated and large activation of executive caspases was observed. The extent of acetylation in the cell is affected by histonedeacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). Combination of SAHA with decitabine brought synergistic effect on apoptosis triggering in CML-T1 cell line, but apoptosis as well as necrosis occured also in normal peripheral blood lymphocytes. Therefore, promising potential of such combined therapy calls for more detailed investigation of unwanted effects in normal cells.

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Acknowledgments

This work was supported by the grant NS-9374-6 from the Ministry of Health of the Czech Republic and the grant No 301/09/1026 from the Grant Agency of the Czech Republic.

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  1. Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20, Prague 2, Czech Republic

    Barbora Brodská, Petra Otevřelová & Aleš Holoubek

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  1. Barbora Brodská
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Correspondence to Barbora Brodská.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s11010-012-1259-1.

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Brodská, B., Otevřelová, P. & Holoubek, A. Decitabine-induced apoptosis is derived by Puma and Noxa induction in chronic myeloid leukemia cell line as well as in PBL and is potentiated by SAHA. Mol Cell Biochem 350, 71–80 (2011). https://doi.org/10.1007/s11010-010-0683-3

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