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Chronic Myeloproliferative Disorders

The anticancer drug imatinib induces cellular autophagy

Leukemia volume 21, pages 936–942 (2007)Cite this article

Abstract

The tyrosine kinase inhibitor imatinib (Gleevec, Novartis Pharmaceuticals Corporation; Basel, Switzerland) is a powerful drug for treatment of chronic myelogenous leukemia (CML) and other malignancies. It selectively targets various tyrosine kinases, thereby leading to growth arrest of respective cancer cells. Given its wide application, it is of high importance to know all related underlying molecular mechanisms. We had previously found that imatinib increases the cellular clearance of intracellular protein aggregates by targeting the abl pathway and thereby upregulating lysosomal activity. Here, we describe that imatinib dose dependently activates the cellular autophagy machinery in mammalian cells, independently of tissue type, species origin or immortalization status of cells. Autophagy is an archetypical cellular degradation mechanism implicated in many physiological and pathophysiological conditions. Our data link for the first time the process of autophagy with the mode of action of imatinib. Induction of autophagy might represent an additional mechanism of imatinib to induce growth arrest, promote apoptosis in cancer cells and eventually even promote tumour regression.

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Acknowledgements

We thank Dr Max Nunziante for helpful discussions and critically reading of the manuscript. This work was supported by the SFB-596 (project A8), FORPRION grant number LMU 5* and the DFG (SCHA 594/3-4), and was performed within the framework of the EU FP6 Network of Excellence Neuroprion.

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Authors and Affiliations

  1. Institute of Virology, Technical University of Munich, Munich, Germany

    A Ertmer, V Huber, S Gilch, V Erfle & H M Schätzl

  2. Department of Cell Genetics, National Institute of Genetics, Mishima, Shizuoka-ken, Japan

    T Yoshimori

  3. Department of Internal Medicine III, Technical University of Munich, Munich, Germany

    J Duyster

  4. Institute of Cytobiology and Cytopathology, Philipps-University of Marburg, Marburg, Germany

    H-P Elsässer

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  1. A Ertmer
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Correspondence to H M Schätzl.

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Ertmer, A., Huber, V., Gilch, S. et al. The anticancer drug imatinib induces cellular autophagy. Leukemia 21, 936–942 (2007). https://doi.org/10.1038/sj.leu.2404606

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