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Staurosporine analogs promote distinct patterns of process outgrowth and polyploidy in small cell lung carcinoma cells

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Tumor Biology

Abstract

We have recently shown that staurosporine mediates the conversion of small cell lung carcinoma (SCLC) cells into a neuron-like process-bearing phenotype. Here, we have extended these studies to the staurosporine analogs K252a, lestaurtinib, PKC412, stauprimide, and UCN-01 and analyzed their influence on process extension, cell cycle distribution, and induction of polyploidy in four SCLC cell lines. In GLC-2 cells, all compounds provoked extensive process formation with the exception of PKC412 that showed no response. In H1184 cells, process formation was predominantly induced by staurosporine and, to lesser extent, in lestaurtinib-, stauprimide-, and UCN-01-treated cells. In the presence of K252a or PKC412, cells became bipolar and spindle shaped or showed pronounced cell flattening. In GLC-36 and SCLC-24H cells, only cell flattening was detectable. Process formation was reversible upon drug removal as shown for GLC-2 and H1184 cells. Fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization (FISH) analysis indicated the induction of polyploidy in all staurosporine and in two out of four stauprimide-treated SCLC cell lines. For other staurosporine analogs, polyploidy was observed only in UCN-01-treated GLC-36 cells and in K252a-treated H1184 and GLC-36 cells. The presence of staurosporine or its analogs did not alter the constitutive activation pattern of the canonical Akt/PI3K or MEK/extracellular signal-regulated kinase (ERK)1/2 signaling pathways nor could we detect an influence of stauprimide application on the expression level of the c-Myc oncogene. These data demonstrate that in SCLC cells, albeit a higher substrate specificity, staurosporine analogs can induce staurosporine-comparable effects.

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Authors and Affiliations

  1. Department of Hematology/Oncology, University of Bonn, Bonn, Germany

    Hichem Gallala & Viktor Janzen

  2. Oral Cell Biology Group, Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany

    Jochen Winter

  3. Neuro- and Tumor Cell Biology Group, Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany

    Nadine Veit & Rainer Probstmeier

  4. Department of Prostate Cancer Research, Institute of Pathology, University of Bonn, Bonn, Germany

    Michael Nowak & Sven Perner

  5. Institute of Legal Medicine, University of Bonn, Bonn, Germany

    Cornelius Courts

  6. Department of Prosthodontics, Preclinical Education, and Material Science, University of Bonn, Bonn, Germany

    Dominik Kraus

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  1. Hichem Gallala
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  2. Jochen Winter
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  3. Nadine Veit
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  4. Michael Nowak
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Correspondence to Rainer Probstmeier.

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Hichem Gallala and Jochen Winter have contributed an equal amount of work.

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Gallala, H., Winter, J., Veit, N. et al. Staurosporine analogs promote distinct patterns of process outgrowth and polyploidy in small cell lung carcinoma cells. Tumor Biol. 36, 2725–2735 (2015). https://doi.org/10.1007/s13277-014-2897-6

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  • DOI: https://doi.org/10.1007/s13277-014-2897-6

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