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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Regulation of TRAIL-induced apoptosis by transcription factors

R Göke1, A Göke, B Göke

  • 1Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Cellular Immunology
|June 1, 2000
PubMed

Insights

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) promotes tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell death, while nuclear factor kappa B (NF-kappaB) inhibits it. PPAR-gamma agonists and NF-kappaB inhibitors enhance TRAIL

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in tumor cells.
  • Mechanisms regulating TRAIL-induced apoptosis in different cell types are not fully understood.

Purpose of the Study:

  • To investigate the distinct roles of peroxisome proliferator-activated receptor (PPAR)-gamma and nuclear factor (NF)-kappaB in regulating TRAIL-induced apoptosis.
  • To identify potential therapeutic targets for enhancing TRAIL-mediated anti-cancer effects.

Main Methods:

  • Activation of PPAR-gamma using its agonist, pioglitazone.
  • Inhibition of NF-kappaB using sulfasalazine.
  • Assessment of TRAIL-induced apoptosis, cell proliferation, and cell cycle progression.

Main Results:

  • Activation of PPAR-gamma significantly enhanced TRAIL-induced apoptosis, accompanied by inhibited proliferation and cell cycle progression.
  • Inhibition of NF-kappaB also significantly enhanced TRAIL-induced apoptosis.
  • These findings indicate that PPAR-gamma promotes and NF-kappaB inhibits TRAIL-induced apoptosis.

Conclusions:

  • Transcription factor PPAR-gamma plays a pro-apoptotic role in TRAIL signaling.
  • Transcription factor NF-kappaB acts as an inhibitor of TRAIL-induced apoptosis.
  • PPAR-gamma agonists and NF-kappaB inhibitors represent promising strategies to potentiate TRAIL-based cancer therapies.

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