title: PPARγ agonists regulate the expression of stemness and differentiation genes in brain tumour stem cells.
abstract: BACKGROUND
  Brain tumour stem cells (BTSCs) are a small population of cancer cells that exhibit self-renewal, multi-drug resistance, and recurrence properties. We have shown earlier that peroxisome proliferator-activated receptor gamma (PPARγ) agonists inhibit the expansion of BTSCs in T98G and U87MG glioma. In this study, we analysed the influence of PPARγ agonists on the expression of stemness and differentiation genes in BTSCs.
  
  
  METHODS
  The BTSCs were isolated from T98G and DB29 glioma cells, and cultured in neurobasal medium with epidermal growth factor+basic fibroblast growth factor. Proliferation was measured by WST-1 (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2 H-5-tetrazolio]-1,3-benzene disulphonate) and 3H thymidine uptake assays, and gene expression was analysed by quantitative reverse--transcription PCR and Taqman array. The expression of CD133, SRY box 2, and nanog homeobox (Nanog) was also evaluated by western blotting, immunostaining, and flow cytometry.
  
  
  RESULTS
  We found that PPARγ agonists, ciglitazone and 15-deoxy-Δ(12,14)-ProstaglandinJ(2), inhibited cell viability and proliferation of T98G- and DB29-BTSCs. The PPARγ agonists reduced the expansion of CD133(+) BTSCs and altered the expression of stemness and differentiation genes. They also inhibited Sox2 while enhancing Nanog expression in BTSCs.
  
  
  CONCLUSIONS
  These findings highlight that PPARγ agonists inhibit BTSC proliferation in association with altered expression of Sox2, Nanog, and other stemness genes. Therefore, targeting stemness genes in BTSCs could be a novel strategy in the treatment of glioblastoma.
authors.affiliation: Neuroscience Research Laboratory, Methodist Research Institute, Indiana University Health, 1800 North Capitol Avenue, Noyes Building E504C, Indianapolis, IN 46202, USA.
authors.forename: E
authors.initials: E
authors.lastname: Pestereva
authors.forename: S
authors.initials: S
authors.lastname: Kanakasabai
authors.forename: J J
authors.initials: JJ
authors.lastname: Bright
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy / Q000473:pathology; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects*; D047495:PPAR gamma / Q000819:agonists*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000032:analysis
chemical_list: D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D047495:PPAR gamma; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors