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  • Original Paper
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Staurosporine and conventional anticancer drugs induce overlapping, yet distinct pathways of apoptosis and caspase activation

Oncogene volume 20, pages 1193–1202 (2001)Cite this article

Abstract

Apoptosis can be induced by various stimuli including DNA-damaging anticancer drugs and the protein kinase inhibitor staurosporine. It is generally believed that the molecular events during execution of apoptosis are shared, as both anticancer drugs and staurosporine derivatives induce mitochondrial damage, cytochrome c release and the activation of the caspase-9 proteolytic cascade. In the present study we show that overexpression of a dominant-negative caspase-9 mutant abolished the activation of endogenous caspase-9, caspase-3 and the cleavage of the caspase substrate Bid in response to anticancer drug treatment. Surprisingly, however, only marginal effects were observed during staurosporine-induced apoptosis. Furthermore, we describe a Jurkat T-cell clone that is completely resistant towards different anticancer drugs, but remains sensitive towards staurosporine-induced apoptosis. In these cells only staurosporine, but neither anti-CD95 nor anticancer drugs were able to trigger caspase activity and the cleavage of caspase substrates. Our results therefore suggest that the mechanism of staurosporine-induced apoptosis is more complex and at least partially differs from anticancer drug-induced caspase activation. These distinct features of staurosporine may allow to bypass chemoresistance of tumor cells and may encourage further clinical trials for the use of staurosporine derivatives in antitumor therapy.

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Acknowledgements

The authors wish to thank Drs ES Alnemri, J Yuan and H Wajant for providing many valuable reagents. This work was supported by grants from the Federal Ministry of Education, Science, Research and Technology and the Interdisciplinary Centers of Clinical Research Center (IZKF) of the Universities of Tübingen and Münster.

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Author notes

  1. Anna Stepczynska and Kirsten Lauber: A Stepczynska and K Lauber share equal first authorship

  2. Sebastian Wesselborg and Klaus Schulze-Osthoff: S Wesselborg and K Schulze-Osthoff share equal senior authorship

Authors and Affiliations

  1. Department of Immunology and Cell Biology, University of Münster, Germany

    Anna Stepczynska, Ingo H Engels & Klaus Schulze-Osthoff

  2. Department of Internal Medicine I, University of Tübingen, Germany

    Kirsten Lauber & Sebastian Wesselborg

  3. Institute of Immunology, University of Kiel, Germany

    Ottmar Janssen & Dieter Kabelitz

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  1. Anna Stepczynska
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Stepczynska, A., Lauber, K., Engels, I. et al. Staurosporine and conventional anticancer drugs induce overlapping, yet distinct pathways of apoptosis and caspase activation. Oncogene 20, 1193–1202 (2001). https://doi.org/10.1038/sj.onc.1204221

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