Sodium selenite induces apoptosis by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in human acute promyelocytic leukemia NB4 cells

Apoptosis. 2009 Feb;14(2):218-25. doi: 10.1007/s10495-008-0295-5.

Abstract

Introduction: In this study, we delineated the apoptotic signaling pathways activated by sodium selenite in NB4 cells.

Materials and methods: NB4 cells were treated with 20 microM sodium selenite for different times. The activation of caspases and ER stress markers, ROS levels, mitochondrial membrane potential and cell apoptosis induced by sodium selenite were analyzed by immunoblotting analysis, DCF fluorescence and flow cytometric respectively. siRNA was used to detect the effect of GADD153 on selenite-induced cell apoptosis.

Conclusions: Sodium selenite-induced reactive oxygen species generation is an early event that triggers endoplasmic reticulum stress mitochondrial apoptotic pathways in NB4 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / pathology*
  • Enzyme Activation / drug effects
  • Humans
  • Leukemia, Promyelocytic, Acute / enzymology
  • Leukemia, Promyelocytic, Acute / pathology*
  • Mitochondria / drug effects
  • Mitochondria / pathology*
  • Models, Biological
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • RNA, Small Interfering / metabolism
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Sodium Selenite / pharmacology*
  • Transcription Factor CHOP / metabolism

Substances

  • DDIT3 protein, human
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Transcription Factor CHOP
  • Proto-Oncogene Proteins c-akt
  • Caspases
  • Sodium Selenite