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

Bhupesh Parashar, Sai Latha Shankar, Kathleen O'Guin, James Butler, Bhadrasain Vikram, Bridget Shafit-Zagardo

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalJournal of Neuro-Oncology
Volume71
Issue number2
DOIs
StatePublished - Jan 1 2005

Keywords

  • Apoptosis
  • CAY10404
  • Cox-2
  • Neuroblastomas
  • Prostaglandins
  • Radiation
  • Survivin

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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