PPARγ agonists inhibit growth and expansion of CD133+ brain tumour stem cells

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 (PPARg) 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 þ BTSC by culturing U87MG and T98G human glioblastoma cells with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). In vitro treatment with PPARg agonist, 15-Deoxy-D 12,14 -Prostaglandin J 2 (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 PPARg in gliosphere cells. These findings demonstrate that PPARg agonists regulate growth and expansion of BTSCs and extend their use to target BTSCs in the treatment of brain tumour.

CD147 reprograms fatty acid metabolism in hepatocellular carcinoma cells through Akt/mTOR/SREBP1c and P38/PPARα pathways

“…Previous studies have provided evidence for a protective role for PPARs against cancer [39][40][41]. Highly consistently, our study found that CD147 suppressed FAO via down-regulating the expression of PPARα and its target genes of CPT1A and ACOX1.…”

Aberrant Notch signaling in glioblastoma stem cells contributes to tumor recurrence and invasion

“…The gliosphere formation assay was performed according to the procedure of a previous study (14). After seven days of culture, the numbers of spheres generated from SP and non-Sp cells were counted.…”

Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells

“…We sorted SP and non-SP cells and then inoculated them into nude mice subcutaneously, but could not detect differences between them in tumourigenisity (data not shown). We next examined CD133, which has been reported to be a cancer stem cell marker (Singh et al, 2003;Hermann et al, 2007;Ricci-Vitiani et al, 2007;Chearwae and Bright, 2008;Mizrak et al, 2008). KYM-1 cells also included a small proportion of CD133-positive cells.…”