The synthetic ligand of peroxisome proliferator-activated receptor-gamma ciglitazone affects human glioblastoma cell lines.
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)-gamma can induce differentiation and inhibit proliferation of several cancer cells. In this study, we have investigated whether one PPARgamma 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 PPARgamma 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 G(1) phase and partial block in G(2)/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, PPARgamma 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.
Department of Pathology and Laboratory of Molecular Pathology, Faculty of Medicine, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic. Nicol.Strakova@seznam.cz
Nicol
N
Strakova
Jiri
J
Ehrmann
Petr
P
Dzubak
Jan
J
Bouchal
Zdenek
Z
Kolar
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000819:agonists* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; C039671:ciglitazone