WWOX-mediated apoptosis in A549 cells mainly involves the mitochondrial pathway

Mol Med Rep. 2012 Jul;6(1):121-4. doi: 10.3892/mmr.2012.860. Epub 2012 Apr 6.

Abstract

The human WWOX gene, known as WW domain-containing oxidoreductase, is located on 16q23.3-24.1, a chromosome region that spans the common fragile site, FRA16D. Abnormal transcripts or even loss of expression are frequently found in a number of cancer cell types, including breast, ovarian, prostate and lung cancer cells. It has therefore been proposed that the WWOX gene encodes a candidate tumor suppressor, possibly a pro-apoptotic protein. However, the mechanism behind this is not entirely clear. In the present study, we examined the pro-apoptotic action of WWOX using transient expression in A549 cells. We observed that the ectopic expression of WWOX caused apoptosis in A549 cells. We further observed procaspase-3 and procaspase-9 activation and the release of cytochrome C from the mitochondria in A549 cells transfected with pcDNA3.0-WWOX. These data indicate that WWOX induces apoptosis in A549 cells via the mitochondrial pathway.

Keywords: WW domain-containing oxidoreductase; mitochondrion; apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma of Lung
  • Apoptosis*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytochromes c / metabolism
  • Enzyme Activation / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Mitochondria / metabolism*
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Signal Transduction*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • WW Domain-Containing Oxidoreductase

Substances

  • Tumor Suppressor Proteins
  • Cytochromes c
  • Oxidoreductases
  • WW Domain-Containing Oxidoreductase
  • WWOX protein, human
  • Caspase 3
  • Caspase 9