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

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 (PPARγ) 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 PPARγ agonist, 15-Deoxy-Δ12,14-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 PPARγ in gliosphere cells. These findings demonstrate that PPARγ agonists regulate growth and expansion of BTSCs and extend their use to target BTSCs in the treatment of brain tumour.

• Publication year

  2008

• Venue

  British Journal of Cancer

• Publication date

  2008-11-18

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/sj.bjc.6604786PMID 19018263PMCID 2607234
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Inhibition of Glioblastoma Growth in a Highly Invasive Nude Mouse Model Can Be Achieved by Targeting Epidermal Growth Factor Receptor but not Vascular Endothelial Growth Factor Receptor-2

  2008cited by this paper
• Tumor Environment Dictates Medulloblastoma Cancer Stem Cell Expression and Invasive Phenotype

  2008cited by this paper
• Caspase-9 pathway activation by inhibiting endogenous fibroblast growth factor signaling in human glioma cells.

  2008cited by this paper
• Targeting brain-tumor stem cells

  2007cited by this paper
• The fibroblast growth factor-2 antisense gene inhibits nuclear accumulation of FGF-2 and delays cell cycle progression in C6 glioma cells.

  2007cited by this paper
• Stem cell-like cancer cells in cancer cell lines

  2007cited by this paper
• Chemotherapeutic options for primary brain tumors

  2006cited by this paper
• Antineoplastic effects of rosiglitazone and PPARγ transactivation in neuroblastoma cells

  2006cited by this paper
• Current therapeutic approaches in patients with brain metastases

  2006cited by this paper
• Targeting the EGFR pathway for cancer therapy.

  2006cited by this paper
• Trigeminal and occipital peripheral nerve stimulation for craniofacial pain: a single-institution experience and review of the literature.

  2006cited by this paper
• Inhibition of in Vivo Glioma Growth and Invasion by Peroxisome Proliferator-Activated Receptor γ Agonist Treatment

  2006cited by this paper
• 15-Deoxy-delta12,14-prostaglandin J2 regulates leukemia inhibitory factor signaling through JAK-STAT pathway in mouse embryonic stem cells.

  2006cited by this paper
• Trends in brain cancer incidence and survival in the United States: Surveillance, Epidemiology, and End Results Program, 1973 to 2001.

  2006cited by this paper
• Glioma stem cells promote radioresistance by preferential activation of the DNA damage response

  2006cited by this paper
• Peroxisome proliferator-activated receptors (PPAR) agonists affect cell viability, apoptosis and expression of cell cycle related proteins in cell lines of glial brain tumors.

  2005cited by this paper
• The Synthetic Ligand of Peroxisome Proliferator-Activated Receptor-γ Ciglitazone Affects Human Glioblastoma Cell Lines

  2004cited by this paper
• Identification of human brain tumour initiating cells

  2004cited by this paper
• The PPARgamma ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines.

  2004cited by this paper
• A novel PPAR alpha/gamma dual agonist inhibits cell growth and induces apoptosis in human glioblastoma T98G cells.

  2004cited by this paper
• The PPARγ ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines

  2004cited by this paper
• 15d-PGJ2 and Rosiglitazone Suppress Janus Kinase-STAT Inflammatory Signaling through Induction of Suppressor of Cytokine Signaling 1 (SOCS1) and SOCS3 in Glia*

  2003cited by this paper
• Peroxisome proliferator-activated receptor-gamma-deficient heterozygous mice develop an exacerbated neural antigen-induced Th1 response and experimental allergic encephalomyelitis.

  2003cited by this paper
• Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis

  2003cited by this paper
• Peroxisome Proliferator-Activated Receptor-γ-Deficient Heterozygous Mice Develop an Exacerbated Neural Antigen-Induced Th1 Response and Experimental Allergic Encephalomyelitis 1

  2003cited by this paper
• Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARγ

  2002cited by this paper
• Signalling, cell cycle and pluripotency in embryonic stem cells.

  2002cited by this paper
• Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARgamma.

  2002cited by this paper
• Embryonic stem cell-derived neurogenesis. Retinoic acid induction and lineage selection of neuronal cells.

  2001cited by this paper
• Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor

  2001cited by this paper
• 15-deoxy-delta(12,14)-PGJ(2) induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats.

  2000cited by this paper
• Direct isolation of human central nervous system stem cells.

  2000cited by this paper
• 15-deoxy-Δ12,14-PGJ2 induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats

  2000cited by this paper
• The search for neural progenitor cells: prospects for the therapy of neurodegenerative disease.

  1999cited by this paper
• Fibroblast growth factors as multifunctional signaling factors.

  1999cited by this paper
• EGF receptor.

  1999cited by this paper
• Essential role of STAT3 for embryonic stem cell pluripotency.

  1999cited by this paper
• From neural stem cells to myelinating oligodendrocytes.

  1999cited by this paper
• Effect of troglitazone in insulin-treated patients with type II diabetes mellitus. Troglitazone and Exogenous Insulin Study Group.

  1998cited by this paper
• Orphan nuclear receptors--new ligands and new possibilities.

  1998cited by this paper
• Basic fibroblast growth factor expression as a predictor of prognosis in pediatric high-grade gliomas.

  1997cited by this paper
• Survival, integration, and differentiation of neural stem cell lines after transplantation to the adult rat striatum.

  1997cited by this paper
• Differentiation of epidermal growth factor-responsive neural precursor cells within neurospheres.

  1996cited by this paper
• 15-Deoxy-Δ12,14-Prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ

  1995cited by this paper
• An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor γ (PPARγ) (*)

  1995cited by this paper
• An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma).

  1995cited by this paper
• Sulfated Glycans Stimulate Endocytosis of the Cellular Isoform of the Prion Protein, PrPC, in Cultured Cells (*)

  1995cited by this paper
• 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma.

  1995cited by this paper
• Fibrolast growth factors in the nervous system

  1994cited by this paper
• Fibroblast growth factors in the nervous system.

  1994cited by this paper
• Basic fibroblast growth factor and fibroblast growth factor receptor I are implicated in the growth of human astrocytomas

  1994cited by this paper
• Repair of demyelinated lesions by transplantation of purified 0-2A progenitor cells

  1993cited by this paper
• Correlation of basic fibroblast growth factor expression levels with the degree of malignancy and vascularity in human gliomas.

  1992cited by this paper
• Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors

  1992cited by this paper
• Localization of basic fibroblast growth factor and its mRNA after CNS injury.

  1991cited by this paper
• Immunohistochemical localization of basic fibroblast growth factor in astrocytomas.

  1990cited by this paper
• Elevated expression of basic fibroblast growth factor messenger ribonucleic acid in acoustic neuromas.

  1989cited by this paper
• Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds.

  1988cited by this paper

• Harnessing the connection of the Wnt/beta-catenin pathway and other signaling pathways in glioblastoma multiforme.

  2026cites this paper
• The Emerging Role of Peroxisome Proliferator-Activated Receptors in Cancer Stemness

  2025cites this paper
• Unlocking therapeutic potential: Exploring nuclear receptors in brain cancer treatment

  2025cites this paper
• Inhibition of hypoxic exosomal miR-423-3p decreases glioma progression by restricting autophagy in astrocytes

  2025cites this paper
• Cut the fat: targeting cholesterol and lipid metabolism in glioblastoma

  2025cites this paper
• The inactive X chromosome drives sex differences in microglial inflammatory activity in human glioblastoma

  2024cites this paper
• Integrated analyses reveal the prognostic, immunological features and mechanisms of cuproptosis critical mediator gene FDX1 in KIRC

  2023cites this paper
• Multilevel chitosan–gelatin particles loaded with P4HA1 siRNA suppress glioma development

  2023cites this paper
• Potential Therapeutic Effects of Thiazolidinedione on Malignant Glioma

  2022cites this paper
• Peroxisome Proliferator-Activated Receptors and the Hallmarks of Cancer

  2022cites this paper
• Glioma Stem-Like Cells and Metabolism: Potential for Novel Therapeutic Strategies

  2021cites this paper
• Cyclopentenone Prostaglandins: Biologically Active Lipid Mediators Targeting Inflammation

  2021cites this paper
• The Impact of PPARD and PPARG Polymorphisms on Glioma Risk and Prognosis

  2020cites this paper
• Peroxisome proliferator-activated receptor gamma as a theragnostic target for mesenchymal-type glioblastoma patients

  2020cites this paper
• Influence of Lipoxygenase Inhibition on Glioblastoma Cell Biology

  2020cites this paper
• Glioblastoma Cell Migration is Directed by Electrical Signals

  2020cites this paper
• Combined proteomics/miRNomics of dendritic cell immunotherapy-treated glioblastoma patients as a screening for survival-associated factors

  2020cites this paper
• ANNALS OF THE NEW YORK ACADEMY OF SCIENCES MARROW

  2019cites this paper
• 15-Deoxy-∆-12,14-Prostaglandin J2 (15d-PGJ2), an Endogenous Ligand of PPAR-γ: Function and Mechanism

  2019cites this paper
• of Regenerative Medicine CD133 Clinical Trials: Safety and Efficacy

  2019cites this paper
• Expression of peroxisome proliferator-activated receptor ( PPAR ) family and survival analysis in patients with multiple myeloma using microarray gene expression profiles

  2019cites this paper
• Spheroid glioblastoma culture conditions as antigen source for dendritic cell-based immunotherapy: spheroid proteins are survival-relevant targets but can impair immunogenic interferon γ production.

  2019cites this paper
• The pan‐cancer mutational landscape of the PPAR pathway reveals universal patterns of dysregulated metabolism and interactions with tumor immunity and hypoxia

  2019cites this paper
• Pan-cancer mutational landscape of the PPAR pathway reveals universal patterns of dysregulated metabolism and interactions with tumor immunity and hypoxia

  2019cites this paper
• Identification of Secreted phosphoprotein 1 (SPP1) as a prognostic factor in lower-grade gliomas.

  2019cites this paper
• Opposite Interplay Between the Canonical WNT/β-Catenin Pathway and PPAR Gamma: A Potential Therapeutic Target in Gliomas

  2018cites this paper
• Gliomasphere marker combinatorics: multidimensional flow cytometry detects CD44+/CD133+/ITGA6+/CD36+ signature

  2018cites this paper
• 15d-PGJ2 is a new hope for controlling tumor growth.

  2018cites this paper
• The influence of peroxisome proliferator-activated receptor γ (PPARγ) ligands on cancer cell tumorigenicity.

  2018cites this paper
• PGD2/PTGDR2 Signaling Restricts the Self‐Renewal and Tumorigenesis of Gastric Cancer

  2018cites this paper
• Thermodynamics in Gliomas: Interactions between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma

  2017cites this paper
• Combination Treatment with PPARγ Ligand and Its Specific Inhibitor GW9662 Downregulates BIS and 14-3-3 Gamma, Inhibiting Stem-Like Properties in Glioblastoma Cells

  2017cites this paper
• Energy metabolism in glioblastoma stem cells: PPARα a metabolic adaptor to intratumoral microenvironment

  2017cites this paper
• PPARγ is correlated with prognosis of epithelial ovarian cancer patients and affects tumor cell progression in vitro

  2017cites this paper
• Physiological and Pathological Roles of 15-Deoxy-Δ12,14-Prostaglandin J2 in the Central Nervous System and Neurological Diseases

  2017cites this paper
• Peroxisome Proliferator-Activated Receptor-γ and Its Ligands in the Treatment of Tumors in the Nervous System.

  2016cites this paper
• Pioglitazone Effect on Glioma Stem Cell Lines: Really a Promising Drug Therapy for Glioblastoma?

  2016cites this paper
• BIS-mediated STAT3 stabilization regulates glioblastoma stem cell-like phenotypes

  2016cites this paper
• Aberrant Notch signaling in glioblastoma stem cells contributes to tumor recurrence and invasion.

  2016cites this paper
• Targeting glioblastoma stem cells (GSCs) with peroxisome proliferator‐activated receptor gamma (PPARγ) ligands

  2016cites this paper
• Expression and Function of PPARs in Cancer Stem Cells.

  2016cites this paper
• Dietary Lutein Modulates Growth and Survival Genes in Prostate Cancer Cells

  2015cites this paper
• Elevation of miR-27 b by HPV 16 E 7 inhibits PPARγ expression and promotes proliferation and invasion in cervical carcinoma cells

  2015cites this paper
• Elevation of miR-27b by HPV16 E7 inhibits PPARγ expression and promotes proliferation and invasion in cervical carcinoma cells.

  2015cites this paper
• CD147 reprograms fatty acid metabolism in hepatocellular carcinoma cells through Akt/mTOR/SREBP1c and P38/PPARα pathways.

  2015cites this paper
• The peroxisome proliferator activated receptor gamma agonist pioglitazone increases functional expression of the glutamate transporter excitatory amino acid transporter 2 (EAAT2) in human glioblastoma cells

  2015cites this paper
• A novel treatment strategy for glioblastoma multiforme and glioma associated seizures: increasing glutamate uptake with PPARγ agonists.

  2015cites this paper
• Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer

  2015cites this paper
• Characterization of fenofibrate-mediated anti-proliferative pro-apoptotic effects on high-grade gliomas and anti-invasive effects on glioma stem cells

  2014cites this paper
• Chemopreventive drugs : Mechanisms via inhibition of cancer stem cells in colorectal cancer

  2014cites this paper
• Chemopreventive drugs: mechanisms via inhibition of cancer stem cells in colorectal cancer.

  2014cites this paper
• Nonsteroidal anti‐inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer

  2014influential citation
• Biological Rationale for the Use of PPARγ Agonists in Glioblastoma

  2014influential citation
• MicroRNAs regulate both epithelial-to-mesenchymal transition and cancer stem cells

  2014cites this paper
• Brain Tumor Stemness

  2013cites this paper
• In silico Analysis of Transcription Factors Associated to Differentially Expressed Genes in Irradiated Glioblastoma Cell Lines

  2013cites this paper
• PPARγ maintains ERBB2-positive breast cancer stem cells

  2013cites this paper
• Enhanced cell growth and tumorigenicity of rat glioma cells by stable expression of human CD133 through multiple molecular actions

  2013cites this paper
• Current Understanding on EGFR and Wnt/β-Catenin Signaling in Glioma and Their Possible Crosstalk.

  2013cites this paper
• Brg1 determines urothelial cell fate during ureter development.

  2013cites this paper
• Functions of neurotrophins and growth factors in neurogenesis and brain repair

  2013cites this paper
• Lycopene modulates growth and survival associated genes in prostate cancer.

  2013cites this paper
• L'activation des récepteurs activés par les proliférateurs de peroxysomes β/δ, stimule l'expression de Siah-1L et entraîne la prolifération et la migration de cellules de glioblastomes

  2013cites this paper
• Tissue Distribution and Versatile Functions of PPARs

  2013cites this paper
• Pregnane xenobiotic receptor in cancer pathogenesis and therapeutic response.

  2013cites this paper
• Leptin and peroxisome proliferator-activated receptor γ expression in colorectal adenoma.

  2012cites this paper
• PPAR Could Contribute to the Pathogenesis of Hepatocellular Carcinoma

  2012cites this paper
• Cancer stem cell-suppressing effect of nonsteroidal anti-inflammatory drugs via cyclooxygenase-2-dependent and -independent pathways in colorectal cancer

  2012cites this paper
• PPAR gamma, bioactive lipids, and cancer progression.

  2012cites this paper
• Changes in the expression of proteins associated with aerobic glycolysis and cell migration are involved in tumorigenic ability of two glioma cell lines

  2012cites this paper
• The PPAR-γ agonist troglitazone antagonizes survival pathways induced by STAT-3 in recombinant interferon-β treated pancreatic cancer cells.

  2012cites this paper
• Progenitores de los tumores cerebrales.

  2012cites this paper
• The influence of peroxisome proliferator-activated receptor γ(1) during differentiation of mouse embryonic stem cells to neural cells.

  2012cites this paper
• PPARγ agonists regulate the expression of stemness and differentiation genes in brain tumour stem cells

  2012cites this paper
• Potential role for STAT3 inhibitors in glioblastoma.

  2012cites this paper
• Mechanistic Insight Into the Role of FABP7 in Malignant Glioma

  2012cites this paper
• Is CD133 a Biomarker for Cancer Stem Cells of Colorectal Cancer and Brain Tumors? A Meta-Analysis

  2011cites this paper
• Targeting inflammation-induced transcription factor activation: an open frontier for glioma therapy.

  2011cites this paper
• Proteomics revisits the cancer metabolome

  2011cites this paper
• Stem cells in brain tumorigenesis and their impact on therapy.

  2011cites this paper
• Understanding the role of tumor stem cells in glioblastoma multiforme: a review article

  2011cites this paper
• Increased Expression of PPARγ1 in the Differentiation of Mouse Embryonic Stem Cells into Definitive Endoderm

  2011cites this paper
• Peroxisome proliferator‐activated receptors and cancer: challenges and opportunities

  2011cites this paper
• Targeting glioma stem cells: A novel framework for brain tumors

  2011cites this paper
• Is CD 133 a biomarker for cancer stem cells of colorectal cancer and brain tumors ? A meta-analysis

  2011cites this paper
• Regulation of glioblastoma stem cells by retinoic acid: role for Notch pathway inhibition

  2011cites this paper
• Identification of a SOX2-dependent subset of tumor- and sphere-forming glioblastoma cells with a distinct tyrosine kinase inhibitor sensitivity profile

  2011cites this paper
• Constitutive androstane receptor agonist CITCO inhibits growth and expansion of brain tumour stem cells

  2011influential citation
• 15-Deoxy-Δ¹²,¹⁴-prostaglandin J₂, an electrophilic lipid mediator of anti-inflammatory and pro-resolving signaling.

  2011cites this paper
• Anticancer Role of PPARγ Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes

  2010cites this paper
• Could Be Systems-Directed Therapy Approaches Promising in Glioblastoma Patients?

  2010cites this paper
• Differentiation Therapy Exerts Antitumor Effects on Stem-like Glioma Cells

  2010cites this paper
• Brain Fatty Acid-binding Protein and ω-3/ω-6 Fatty Acids

  2010cites this paper
• Cancer stem cell markers: what is their diagnostic value?

  2010cites this paper
• PPARs and Anticancer Therapies

  2010cites this paper
• The Side Population of Gliomas Exhibits Decreased Cell Migration

  2010cites this paper
• STAT3 as a Therapeutic Target for Glioblastoma.

  2010cites this paper
• A Methodological Approach to Personalized Therapies in Metastatic Cancer

  2010cites this paper
• Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells

  2009cites this paper
• Brain cancer stem cells

  2009cites this paper