, Volume 11, Issue 10, pp 1801–1811 | Cite as

PPARγ is a key target of butyrate-induced caspase-3 activation in the colorectal cancer cell line Caco-2

  • Markus Schwab
  • Veerle Reynders
  • Sandra Ulrich
  • Nadine Zahn
  • Jürgen Stein
  • Oliver SchröderEmail author


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 PPARγ mutant cells along the signalling pathway. In this context, the involvement and up-regulation of PPARγ was examined. Results: Stimulation of cells with butyrate resulted in increased expression of PPARγ 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 PPARγ expression, thereby mimicking the effects of butyrate. In contrast, butyrate-mediated up-regulation of PPARγ 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 PPARγ mutant cells. Conclusions: Our data clearly unveil PPARγ as a key target in the butyrate-induced signalling cascade leading to apoptosis via caspase-3 in Caco-2 cells.


Apoptosis Butyrate Caspase-3 p38 MAPK PPARγ 



DNA Fragmentation Factor


Dulbecco’s modified Eagle’s medium


Dimethyl sulfoxide


European Collection of cell cultures


Epithelial growth factor


Extracellular signal-regulated kinase


Foetal calf serum


FLICE-inhibitory protein


Histone deacetylase


Inhibitor of apoptosis protein


cJun N-terminal kinase


Lactate dehydrogenase


Mitogen-activated protein kinase


Poly(ADP-ribose) Polymerase


Phosphate buffered saline


Protein kinase C-δ


Peroxisome proliferator-activated receptor γ


Short chain fatty acid


Signal transducer and activator of transcription-3


Tris-buffered saline containing 0.05% Tween 20


Tumor necrosis factor


X linked inhibitor of apoptosis


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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Markus Schwab
    • 1
  • Veerle Reynders
    • 1
  • Sandra Ulrich
    • 1
  • Nadine Zahn
    • 1
  • Jürgen Stein
    • 1
  • Oliver Schröder
    • 1
    Email author
  1. 1.First Department of Medicine-ZAFESJohann Wolfgang Goethe-University FrankfurtFrankfurt am MainGermany

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