Pioglitazone, a synthetic ligand for PPARgamma, induces apoptosis in RB-deficient human colorectal cancer cells

Apoptosis. 2006 Mar;11(3):401-11. doi: 10.1007/s10495-006-4003-z.


No published data are available about the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and the role of PPARgamma in retinoblastoma protein (RB)-deficient human colorectal cancer (CRC) cells (SNU-C4 and SNU-C2A). Our aim was to investigate whether PPARgamma is expressed in SNU-C4 and SNU-C2A cells and to elucidate possible molecular mechanisms underlying the effect of pioglitazone, a synthetic ligand for PPARgamma, on cell growth in these cell lines. RT-PCR and Western blot analysis showed that both human CRC cell lines expressed PPARgamma mRNA and protein. Pioglitazone inhibited the cell growth of both cell lines through G2/M phase block and apoptosis. In addition, pioglitazone caused a down-regulation of the X chromosome-linked inhibitor of apoptosis (XIAP), Bcl-2, and cyclooxygenase-2 (COX-2) under conditions leading to PPARgamma down-regulation. These results suggest that pioglitazone may have therapeutic relevance or significance in the treatment of human CRC, and the down-regulation of XIAP, Bcl-2, and COX-2 may contribute to pioglitazone-induced apoptosis in these and other RB-deficient cell lines and tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Caspases / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Colorectal Neoplasms / metabolism*
  • Cyclooxygenase 2 / metabolism
  • Cytochromes c / metabolism
  • Enzyme Activation
  • Humans
  • Hypoglycemic Agents / metabolism*
  • Ligands
  • PPAR gamma / metabolism*
  • Pioglitazone
  • Poly(ADP-ribose) Polymerases / metabolism
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*
  • Thiazolidinediones / metabolism*


  • Cell Cycle Proteins
  • Hypoglycemic Agents
  • Ligands
  • PPAR gamma
  • Retinoblastoma Protein
  • Thiazolidinediones
  • Cytochromes c
  • Cyclooxygenase 2
  • Poly(ADP-ribose) Polymerases
  • Caspases
  • Pioglitazone