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The combination of sulfinosine and 8-Cl-cAMP induces synergistic cell growth inhibition of the human neuroblastoma cell line in vitro

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Summary

To identify purine analogs that could be effective in treating neuroblastomas, we tested the anticancer properties of sulfinosine, 8-Cl-cAMP and 8-Cl-adenosine in the SK-N-SH cell line. First we examined the effects of these three agents on cell growth inhibition and cell viability by the BrdU and Sulforhodamine B assay. Treatment of SK-N-SH cells with increasing concentrations of these compounds led to a significant inhibition of cell proliferation and decrease of cell viability in a time- and dose-dependant manner at micromolar concentration (<10 μM). Treatment with a combination of sulfinosine and 8-Cl-cAMP resulted in synergistic effects on growth inhibition, cell cycle arrest and induction of apoptosis. Flow-cytometric analysis showed that 8-Cl-cAMP arrested the cells in the G0/G1 phase and sulfinosine blocked cell cycle progression at the G2/M stage, in contrast to the combined effects of both agents that did not arrest growth at any particular phase of the cell cycle. Further analysis of apoptosis induction demonstrated an increase from 17 to 24% of both early and late apoptotic cells and a very low percentage of necrotic cells. These results indicate that apoptosis was the predominant type of cell death after treatment of SK-N-SH cells with both substances, as well as with their combinations.

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Authors and Affiliations

  1. Department of Neurobiology and Immunology, Institute for Biological Research, Belgrade, 11060, Serbia & Montenegro

    Dragana Janković, Milica Pesić, Jasna Marković, Selma Kanazir & Sabera Ruždijić Ph.D.

  2. Faculty of Medicine, University of Belgrade, Belgrade, 11000, Serbia & Montenegro

    Ivanka Marković

  3. Serbian Academy of Sciences and Arts, Belgrade, 11000, Serbia & Montenegro

    Ljubisav Rakić

  4. Department of Neurobiology and Immunology, Institute for Biological Research, Molecular Neurobiology Laboratory, Bulevar Despota Stefana 142, Belgrade, 11060, Serbia & Montenegro (Former Yugoslavia)

    Sabera Ruždijić Ph.D.

Authors
  1. Dragana Janković
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  2. Milica Pesić
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  3. Jasna Marković
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  4. Selma Kanazir
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  5. Ivanka Marković
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  6. Ljubisav Rakić
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  7. Sabera Ruždijić Ph.D.
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Correspondence to Sabera Ruždijić Ph.D..

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Janković, D., Pesić, M., Marković, J. et al. The combination of sulfinosine and 8-Cl-cAMP induces synergistic cell growth inhibition of the human neuroblastoma cell line in vitro . Invest New Drugs 24, 15–25 (2006). https://doi.org/10.1007/s10637-005-4539-8

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