1. ¹Neuroscience Research Laboratory, Methodist Research Institute at Clarian Health, Indianapolis, IN, USA
2. ²Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

Correspondence: Dr JJ Bright, Methodist Research Institute, 1800 N Capitol Avenue, Noyes Building E-504C, Indianapolis, IN 46202, USA; E-mail: jbright1@clarian.org

Received 30 July 2008; Revised 23 October 2008; Accepted 23 October 2008; Published online 18 November 2008.

Abstract

Brain tumour stem cells (BTSCs) are a small population of cells that has self-renewal, transplantation, multidrug resistance and recurrence properties, thus remain novel therapeutic target for brain tumour. Recent studies have shown that peroxisome proliferator-activated receptor gamma (PPAR) agonists induce growth arrest and apoptosis in glioblastoma cells, but their effects on BTSCs are largely unknown. In this study, we generated gliospheres with more than 50% CD133+ BTSC by culturing U87MG and T98G human glioblastoma cells with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). In vitro treatment with PPAR agonist, 15-Deoxy-^12,14-Prostaglandin J₂ (15d-PGJ2) or all-trans retinoic acid resulted in a reversible inhibition of gliosphere formation in culture. Peroxisome proliferator-activated receptor gamma agonists inhibited the proliferation and expansion of glioma and gliosphere cells in a dose-dependent manner. Peroxisome proliferator-activated receptor gamma agonists also induced cell cycle arrest and apoptosis in association with the inhibition of EGF/bFGF signalling through Tyk2-Stat3 pathway and expression of PPAR in gliosphere cells. These findings demonstrate that PPAR agonists regulate growth and expansion of BTSCs and extend their use to target BTSCs in the treatment of brain tumour.