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Molecular Targets for Therapy

Inhibition of Myb-dependent gene expression by the sesquiterpene lactone mexicanin-I

Leukemia volume 26, pages 615–622 (2012)Cite this article

Abstract

The c-myb proto-oncogene encodes a transcription factor that is highly expressed in the progenitor cells of the hematopoietic system, where it regulates the expression of genes important for lineage determination, cell proliferation and differentiation. There is strong evidence that deregulation of c-myb expression is involved in the development of human tumors, particularly of certain types of leukemia, and breast and colon cancer. The c-Myb protein is therefore an interesting therapeutic target. Here, we have investigated the potential of natural sesquiterpene lactones (STLs), a class of compounds that are active constituents of a variety of medicinal plants, to suppress Myb-dependent gene expression. We have developed a test system that allows screening of compounds for their ability to interfere with the activation of Myb target genes. Using this assay system, we have identified the STL mexicanin-I as the first cell-permeable, low-molecular-weight inhibitor of Myb-induced gene expression.

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Acknowledgements

We thank B Berkenfeld, J Steffen and A Krause for technical assistance, and O Gabrielsen for plasmids. This work was supported by Deutsche José Carreras Leukämie-Stiftung and the Deutsche Forschungsgemeinschaft.

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Author notes

  1. T Bujnicki, C Wilczek and C Schomburg: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute for Biochemistry, Westfälische-Wilhelms-Universität, Münster, Germany

    T Bujnicki, C Wilczek, F Feldmann & K-H Klempnauer

  2. Institute for Pharmaceutical Biology and Phytochemistry, Westfälische-Wilhelms-Universität, Münster, Germany

    C Schomburg & T J Schmidt

  3. Institute for Transfusion Medicine, Westfälische-Wilhelms-Universität, Münster, Germany

    P Schlenke

  4. Department of Medicine A, Hematology and Oncology, Westfälische-Wilhelms-Universität, Münster, Germany

    C Müller-Tidow

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Correspondence to K-H Klempnauer.

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Bujnicki, T., Wilczek, C., Schomburg, C. et al. Inhibition of Myb-dependent gene expression by the sesquiterpene lactone mexicanin-I. Leukemia 26, 615–622 (2012). https://doi.org/10.1038/leu.2011.275

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