Duocarmycin Analogues Target Aldehyde Dehydrogenase 1 in Lung Cancer Cells

Authors

  • M. Sc. Tanja Wirth,

    1. Department Chemie, Center for Integrated Protein Science CIPSM, Institute of Advanced Studies IAS, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
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  • Dr. Kianga Schmuck,

    1. Institute of Organic and Biomolecular Chemistry, Georg-August-Universität Göttingen, Tammannstr. 2, 37033 Göttingen (Germany)
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  • Prof. Dr. Lutz F. Tietze,

    Corresponding author
    1. Institute of Organic and Biomolecular Chemistry, Georg-August-Universität Göttingen, Tammannstr. 2, 37033 Göttingen (Germany)
    • Institute of Organic and Biomolecular Chemistry, Georg-August-Universität Göttingen, Tammannstr. 2, 37033 Göttingen (Germany)
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  • Prof. Dr. Stephan A. Sieber

    Corresponding author
    1. Department Chemie, Center for Integrated Protein Science CIPSM, Institute of Advanced Studies IAS, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
    • Department Chemie, Center for Integrated Protein Science CIPSM, Institute of Advanced Studies IAS, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
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  • We thank Mona Wolff and Burghard Cordes for excellent scientific support and Matthew Nodwell and Nina Mäusbacher for scientific discussions. S.S. was supported by the Deutsche Forschungsgemeinschaft (Emmy Noether), grant numbers SFB749 and FOR1406, an ERC starting grant, and the Center for Integrated Protein Science Munich CIPSM. T.W. thanks the TUM Graduate School for project funding. K.S. thanks the Fonds der Chemischen Industrie for a Ph.D. scholarship. L.F.T thanks the DFG and the Fonds der Chemischen Industrie for financial support.

Abstract

original image

Reacquiring the target: A proteomic profiling approach has been used to show that aldehyde dehydrogenase 1 may be an additional or alternative target of duocarmycin. Selective inhibition of this enzyme in lung cancer cells explains the antitumor activity of duocarmycin analogues (see scheme).

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