Induction of apoptosis in human multiple myeloma cell lines by ebselen via enhancing the endogenous reactive oxygen species production

Biomed Res Int. 2014:2014:696107. doi: 10.1155/2014/696107. Epub 2014 Jan 27.

Abstract

Ebselen a selenoorganic compound showing glutathione peroxidase like activity is an anti-inflammatory and antioxidative agent. Its cytoprotective activity has been investigated in recent years. However, experimental evidence also shows that ebselen causes cell death in several cancer cell types whose mechanism has not yet been elucidated. In this study, we examined the effect of ebselen on multiple myeloma (MM) cell lines in vitro. The results showed that ebselen significantly enhanced the production of reactive oxygen species (ROS) accompanied by cell viability decrease and apoptosis rate increase. Further studies revealed that ebselen can induce Bax redistribution from the cytosol to mitochondria leading to mitochondrial membrane potential ΔΨm changes and cytochrome C release from the mitochondria to cytosol. Furtherly, we found that exogenous addition of N-acetyl cysteine (NAC) completely diminished the cell damage induced by ebselen. This result suggests that relatively high concentration of ebselen can induce MM cells apoptosis in culture by enhancing the production of endogenous ROS and triggering mitochondria mediated apoptotic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Azoles / administration & dosage*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Isoindoles
  • Membrane Potential, Mitochondrial / drug effects
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Organoselenium Compounds / administration & dosage*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • bcl-2-Associated X Protein / biosynthesis

Substances

  • Azoles
  • Isoindoles
  • Organoselenium Compounds
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • ebselen