Essential role for p53 and caspase-9 in DNA damaging drug-induced apoptosis in neuroblastoma IMR32 cells

DNA Cell Biol. 2011 Dec;30(12):1045-50. doi: 10.1089/dna.2011.1255. Epub 2011 May 25.

Abstract

Neuroblastoma is a solid tumor of the sympathetic nervous system accounting for up to 10% of pediatric cancers and 15% of cancer-related deaths. It is a useful system for investigation of stress signal-mediated apoptosis as a tumor suppression mechanism. In this study, we present evidence that p53 mediates DNA damaging drug-induced apoptosis in IMR32 cells through the caspase-9 pathway. In summary, we define a molecular pathway for mediating DNA damaging drug-induced apoptosis in human neuroblastoma IMR32 cells and suggest that inactivation of essential components of this apoptotic pathway may confer drug resistance on neuroblastoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / toxicity
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Caspase 9 / physiology*
  • Cell Line, Tumor / drug effects
  • DNA Damage / physiology
  • DNA, Neoplasm / drug effects
  • Doxorubicin / toxicity
  • Genes, p53
  • Humans
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Neuroblastoma / pathology*
  • RNA Interference
  • RNA, Small Interfering / pharmacology
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Antibiotics, Antineoplastic
  • DNA, Neoplasm
  • Neoplasm Proteins
  • RNA, Small Interfering
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Doxorubicin
  • Caspase 9