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Tumor Biology

, Volume 36, Issue 4, pp 2725–2735 | Cite as

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

  • Hichem Gallala
  • Jochen Winter
  • Nadine Veit
  • Michael Nowak
  • Sven Perner
  • Cornelius Courts
  • Dominik Kraus
  • Viktor Janzen
  • Rainer Probstmeier
Research Article

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.

Keywords

K252a Lestaurtinib PKC412 Small cell lung carcinoma Stauprimide Staurosporine UCN-01 

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Hichem Gallala
    • 1
  • Jochen Winter
    • 2
  • Nadine Veit
    • 3
  • Michael Nowak
    • 4
  • Sven Perner
    • 4
  • Cornelius Courts
    • 5
  • Dominik Kraus
    • 6
  • Viktor Janzen
    • 1
  • Rainer Probstmeier
    • 3
  1. 1.Department of Hematology/OncologyUniversity of BonnBonnGermany
  2. 2.Oral Cell Biology Group, Department of Periodontology, Operative and Preventive DentistryUniversity of BonnBonnGermany
  3. 3.Neuro- and Tumor Cell Biology Group, Department of Nuclear MedicineUniversity of BonnBonnGermany
  4. 4.Department of Prostate Cancer Research, Institute of PathologyUniversity of BonnBonnGermany
  5. 5.Institute of Legal MedicineUniversity of BonnBonnGermany
  6. 6.Department of Prosthodontics, Preclinical Education, and Material ScienceUniversity of BonnBonnGermany

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