Apoptosis induced by troglitazone is both peroxisome proliferator-activated receptor-γ- and ERK-dependent in human non-small lung cancer cells
Article first published online: 1 AUG 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 209, Issue 2, pages 428–438, November 2006
How to Cite
Li, M., Lee, T. W., Yim, A. P.C., Mok, T. S.K. and Chen, G. G. (2006), Apoptosis induced by troglitazone is both peroxisome proliferator-activated receptor-γ- and ERK-dependent in human non-small lung cancer cells. J. Cell. Physiol., 209: 428–438. doi: 10.1002/jcp.20738
- Issue published online: 29 AUG 2006
- Article first published online: 1 AUG 2006
- Manuscript Accepted: 12 JUN 2006
- Manuscript Received: 23 APR 2006
- Research Grants Council of the Hong Kong Special Administrative Region. Grant Number: CUHK 4390/03M
The role of the peroxisome proliferator-activated receptor-gamma (PPARγ) in cell differentiation, cell-cycle arrest, and apoptosis has attracted increasing attention. We have recently demonstrated that PPARγ ligands-troglitazone (TGZ) induced apoptosis in lung cancer cells. In this report, we further studied the role of ERK1/2 in lung cancer cells treated by TGZ. The result demonstrated that TGZ induced PPARγ and ERK1/2 accumulation in the nucleus, in which the co-localization of both proteins was found. The activation of ERK1/2 resulted in apoptosis via a mitochondrial pathway. Both PPARγ siRNA and U0126, a specific inhibitor of ERK1/2, were able to block these effects of TGZ, suggesting that apoptosis induced by TGZ was PPARγ and ERK1/2 dependent. Inhibition of ERK1/2 by U0126 also led to a significant decrease in the level of PPARγ, indicating a positive cross-talk between PPARγ and ERK1/2 or an auto-regulatory feedback mechanism to amplify the effect of ERK1/2 on cell growth arrest and apoptosis. In addition to ERK1/2, TGZ also activated Akt. Interestingly, inhibition of ERK1/2 prevented the activation of Akt whereas the suppression of Akt had no effect on ERK1/2, suggesting that Akt was not necessary for TGZ-PPARγ-ERK pathway. However, the inhibition of Akt promoted the release of cytochrome c, suggesting the activation of Akt may have a negative effect on apoptosis induced by TGZ. In conclusion, our study has demonstrated that TGZ, a synthetic PPARγ ligand, induced apoptosis in NCI-H23 lung cancer cells via a mitochondrial pathway and this pathway was PPARγ and ERK1/2 dependent. J. Cell. Physiol. 209: 428–438, 2006. © 2006 Wiley-Liss, Inc.