Activation of peroxisome proliferator-activated receptor-gamma by troglitazone (TGZ) inhibits human lung cell growth

J Cell Biochem. 2005 Nov 1;96(4):760-74. doi: 10.1002/jcb.20474.


Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and a crucial regulator of cellular differentiation. PPAR-gamma ligands have been demonstrated to inhibit growth of several cancer cells. In this study, two human lung cancer cells (NCI-H23 and CRL-2066) and one human lung normal cell (CRL-202) were used for the experiments. The results showed that in consistence with the loss of viability, troglitazone (TGZ) induced apoptosis of CRL-2066 and NCI-H23 cells but not CCL-202 cells. TGZ upregulated PPAR-gamma expression in all the three lung cell lines, especially in the cancer cells. In association of the time-dependent inhibition of the cell proliferation, TGZ downregulated the expression of Bcl-w and Bcl-2 but activated extracellular signal-regulated kinase (ERK)1/2 and p38, suggesting that the growth-inhibitory effect of TGZ is associated with the reduction of Bcl-w and Bcl-2 and the increase of ERK1/2 and p38 activation. SAPK/JNK activation assay showed a decreased activity in all the three cell lines tested after TGZ treatment. It was also demonstrated that TGZ could activate PPAR-gamma transcriptionally. We conclude that TGZ inhibits growth of human lung cancer cells via the induction of apoptosis and the inhibition of cell growth, at least in part, in a PPAR-gamma-relevant manner. The mechanism of TGZ is associated with the activation of ERK and p38, the reduction of SAPK/JNK activity, and the alteration of Bcl-w and Bcl-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival
  • Chromans / pharmacology*
  • Fibroblasts
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / pathology*
  • MAP Kinase Signaling System / drug effects
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Thiazolidinediones / pharmacology*
  • Transcriptional Activation / genetics*
  • Troglitazone


  • Chromans
  • PPAR gamma
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Thiazolidinediones
  • Troglitazone