Peroxisome proliferator-activated receptor γ ligand troglitazone and TRAIL synergistically induce apoptosis

Oncol Rep. 2014 Feb;31(2):947-54. doi: 10.3892/or.2013.2868. Epub 2013 Nov 25.


Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to cause apoptosis in several types of malignant tumor cells through its interaction with the death domain-containing receptor, death receptor 5 (DR5). In the present study, we showed that co-treatment with troglitazone (TGZ), a synthetic ligand of peroxisome proliferator-activated receptor γ (PPARγ), and TRAIL synergistically induced apoptosis through DR5 upregulation in human colon cancer DLD-1 cells. TGZ elevated DR5 expression at the promoter level through the CCAAT/enhancer-binding protein homologous protein (CHOP) binding site. These results suggest that combined treatment with TGZ and TRAIL may be promising as a new therapy against malignant tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / pharmacology
  • Binding Sites
  • Cell Line, Tumor
  • Chromans / pharmacology*
  • Colonic Neoplasms / pathology
  • Drug Synergism
  • Endoplasmic Reticulum Stress / physiology
  • Humans
  • PPAR gamma
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / biosynthesis
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics*
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Thiazolidinediones / pharmacology*
  • Transcription Factor CHOP / biosynthesis
  • Transcription Factor CHOP / genetics
  • Transcription Factor CHOP / metabolism*
  • Troglitazone


  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Chromans
  • DDIT3 protein, human
  • PPAR gamma
  • RNA, Small Interfering
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNF-Related Apoptosis-Inducing Ligand
  • Thiazolidinediones
  • Transcription Factor CHOP
  • Troglitazone