QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.063438v1 jpet.103.063438v2 309/3/1239    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Strakova, N. Articles by Kolar, Z. Search for Related Content PubMed PubMed Citation Articles by Strakova, N. Articles by Kolar, Z.

CELLULAR AND MOLECULAR

The Synthetic Ligand of Peroxisome Proliferator-Activated Receptor- Ciglitazone Affects Human Glioblastoma Cell Lines

Department of Pathology, Laboratory of Molecular Pathology (N.S., J.E., J.B., Z.K.) and Laboratory of Experimental Medicine (P.D.), Faculty of Medicine, Palacky University, Olomouc, Czech Republic

Glioblastoma multiforme is the most common malignant brain tumor in adults, and it is among the most lethal of all cancers. Recent studies have shown that ligand activation of peroxisome proliferator-activated receptor (PPAR)- can induce differentiation and inhibit proliferation of several cancer cells. In this study, we have investigated whether one PPAR ligand in particular, ciglitazone, inhibits cell viability and, additionally, whether it affects the cell cycle and apoptosis of human glioblastoma cell lines T98G, U-87 MG, A172, and U-118 MG. All glioblastoma cell lines were found to express PPAR protein, and following treatment with ciglitazone, localization was unchanged. Ciglitazone inhibited viability in a dose-dependent manner in all four tested glioblastoma cells after 24 h of treatment. Analysis of the cell cycle showed arrest in the G₁ phase and partial block in G₂/M phase of the cell cycle. Cyclin D1 and cyclin B expression was decreased. Phosphorylation of Rb protein dropped as well. We found that ciglitazone was followed by increased expression of p27^Kip1 and p21^Waf1/Cip1. It also led to apoptosis induction: bax expression in T98G was elevated. Expression of the antiapoptotic protein bcl-2 was reduced in U-118 MG and U-87 MG and showed a slight decrease in A172 cells. Flow cytometry confirmed the induction of apoptosis. Moreover, PPAR ligand decreased telomerase activity in U-87 MG and U-118 MG cell lines. Our results demonstrate that ciglitazone inhibits the viability of human glioblastoma cell lines via induction of apoptosis; as a result, this ligand may offer potential new therapy for the treatment of central nervous system neoplasms.

Address correspondence to: Nicol Strakova, Department of Pathology and Laboratory of Molecular Pathology, Faculty of Medicine, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic. E-mail: Nicol.Strakova{at}seznam.cz

This article has been cited by other articles:

				M. A. Peraza, A. D. Burdick, H. E. Marin, F. J. Gonzalez, and J. M. Peters The Toxicology of Ligands for Peroxisome Proliferator-Activated Receptors (PPAR) Toxicol. Sci., April 1, 2006; 90(2): 269 - 295. [Abstract] [Full Text] [PDF]