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Inhibition of human neuroblastoma cell growth by CAY10404, a highly selective Cox-2 inhibitor

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Abstract

Neuroblastomas constitute about 10% of childhood cancers and are responsible for 15% of pediatric cancer mortality. We evaluated the efficacy and the mechanism of cell death induced by CAY10404, a selective cyclooxygenase-2 (Cox-2) inhibitor in four human neuroblastoma cell lines (SH-EP, SH-SY5Y, SK-N-MC and MSN). Treatment with CAY10404 in the range of 15–115 μM revealed a dose-dependent decrease in cell number and an average IC50 (inhibitory concentration 50%) of 60 μM. About 20–30% of the cells were terminal deoxynucleotidyltransferase-mediated UTP nick-end-labeling (TUNEL) positive 48 h after treatment. Western blot analysis of CAY10404-treated cells showed poly(ADP-ribose) polymerase (PARP) cleavage and cleaved caspase-3 signifying caspase activity and apoptotic cell death. Inhibitor-of-apoptosis proteins including X-linked inhibitor-of-apoptosis protein (XIAP) and survivin did not change significantly after CAY10404 treatment. Fluorescence activated cell sorter (FACS) analysis performed in two different cell lines 48 h following CAY10404 treatment showed a reduction in the number of cells in the G1 phase of the cell cycle and an increase in the number of cells in the G2 phase. When radioresistant SH-EP cells were treated with CAY10404, a 49% decrease in cell viability was observed relative to DMSO-treated cells; pretreatment with CAY10404 followed by ortho-voltage irradiation further enhanced cell death (58%) suggesting radiosensitization by CAY10404.

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Authors and Affiliations

  1. Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY, USA

    Bhupesh Parashar, James Butler & Bhadrasain Vikram

  2. Department of Pathology, Albert Einstein College of Medicine, Forchheimer 524, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Sai Latha Shankar, Kathleen O’Guin & Bridget Shafit-Zagardo

Authors
  1. Bhupesh Parashar
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  2. Sai Latha Shankar
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  3. Kathleen O’Guin
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  4. James Butler
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  5. Bhadrasain Vikram
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  6. Bridget Shafit-Zagardo
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Corresponding author

Correspondence to Bridget Shafit-Zagardo.

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Parashar, B., Latha Shankar, S., O’Guin, K. et al. Inhibition of human neuroblastoma cell growth by CAY10404, a highly selective Cox-2 inhibitor. J Neurooncol 71, 141–148 (2005). https://doi.org/10.1007/s11060-004-1721-3

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  • DOI: https://doi.org/10.1007/s11060-004-1721-3

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