TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000651735
  • Gene Name:PPARG (PPARgamma)
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:PPAR gamma signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB03568 (EXPT00774)
  • Drug Name:Butyric Acid
  • Drug Method:up-regulated the gene expression

Disease basic infommation

  • Disease:colon cancer
  • Tissue:cell line (Caco-2)

Other information

  • Title:PPARgamma is a key target of butyrate-induced caspase-3 activation in the colorectal cancer cell line Caco-2
  • Journal:Apoptosis
  • Published:2006
  • PubMed ID:16927016
  • Abstract:Background:Butyrate, a potent histone deacetylase inhibitor, belongs to a promising new class of antineoplastic agents with the capacity to induce apoptosis of cancer cells. However, the underlying mechanisms of action have yet not been elucidated. Aim:To further investigate the molecular events involved in butyrate-induced caspase-3 activation in Caco-2 wild-type, empty-vector and dominant-negative PPARgamma mutant cells along the signalling pathway. In this context, the involvement and up-regulation of PPARgamma was examined. Results:Stimulation of cells with butyrate resulted in increased expression of PPARgamma mRNA, protein, and activity as well as phospho-p38 MAPK protein expression and caspase-3 activity. Arsenite, a direct stimulator of p38 MAPK, also led to an increased PPARgamma expression, thereby mimicking the effects of butyrate. In contrast, butyrate-mediated up-regulation of PPARgamma was counteracted by co-incubation with the p38 MAPK inhibitor SB203580. Treatment of cells with butyrate resulted in both increased caspase-8 and -9 activity and reduced expression of XIAP and survivin. However, butyrate-mediated effects on these apoptosis-regulatory proteins leading to caspase-3 activation were almost completely abolished in Caco-2 dominant-negative PPARgamma mutant cells. Conclusions:Our data clearly unveil PPARgamma as a key target in the butyrate-induced signalling cascade leading to apoptosis via caspase-3 in Caco-2 cells.
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