PPARγ Agonists Promote Oligodendrocyte Differentiation of Neural Stem Cells by Modulating Stemness and Differentiation Genes

Kanakasabai, Saravanan; Pestereva, E; Chearwae, Wanida; Gupta, Sushil K.; Ansari, Saif; Bright, John J.

doi:10.1371/journal.pone.0050500

Cited by 59 publications

(51 citation statements)

References 71 publications

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“…This is important in the cases of grade III and IV glioma, as the BTSCs may be responsible for the recurrence and growth of the malignant tissue through mechanisms such as self-renewal (35, 36). …”

Section: Current Research Into Pparγ Agonists and Glioblastoma Multifmentioning

confidence: 99%

Biological Rationale for the Use of PPARÎ³ Agonists in Glioblastoma

Ellis

Kurian

2014

Front. Oncol.

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Glioblastoma multiforme (GBM) is the most common primary intrinsic central nervous system tumor and has an extremely poor overall survival with only 10% patients being alive after 5 years. There has been interesting preliminary evidence suggesting that diabetic patients receiving peroxisome proliferator-activated receptor gamma (PPARγ) agonists, a group of anti-diabetic, thiazolidinedione drugs, have an increased median survival for glioblastoma. Although thiazolidinediones are effective oral medications for type 2 diabetes, certain agonists carry the risk for congestive heart failure, myocardial infarction, cardiovascular disease, bone loss, weight gain, and fluid retention as side-effects. The nuclear receptor transcription factor PPARγ has been found to be expressed in high grade gliomas, and its activation has been shown to have several antineoplastic effects on human and rat glioma cell lines, and in some instances an additional protective increase in antioxidant enzymes has been observed in normal astrocytes. At present, no clinical trials are underway with regards to treating glioma patients using PPARγ agonists. This review presents the case for evaluating the potential of PPARγ agonists as novel adjuvants in the treatment of refractory high grade glioma.

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Section: Current Research Into Pparγ Agonists and Glioblastoma Multifmentioning

confidence: 99%

Biological Rationale for the Use of PPARÎ³ Agonists in Glioblastoma

Ellis

Kurian

2014

Front. Oncol.

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“…Activation of PPARγ in lung cancer cell lines has induced differentiation and apoptosis . Additional recent studies provide further evidence demonstrating these agents may be useful in colon, neural, ovarian, melanoma, and lung cancer ; however, mechanisms of downstream action may vary between tissue types. In colon cancer, a principal finding of ciglitazone treatment was alterations in chaperones associated with protein folding .…”

Section: Introductionmentioning

confidence: 97%

Functional activation of PPARγ in human upper aerodigestive cancer cell lines

et al. 2016

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Upper aerodigestive cancer is an aggressive malignancy with relatively stagnant long-term survival rates over 20 yr. Recent studies have demonstrated that exploitation of PPARγ pathways may be a novel therapy for cancer and its prevention. We tested whether PPARγ is expressed and inducible in aerodigestive carcinoma cells and whether it is present in human upper aerodigestive tumors. Human oral cancer CA-9-22 and NA cell lines were treated with the PPAR activators eicosatetraynoic acid (ETYA), 15-deoxy-δ-12,14-prostaglandin J2 (PG-J2), and the thiazolidinedione, ciglitazone, and evaluated for their ability to functionally activate PPARγ luciferase reporter gene constructs. Cellular proliferation and clonogenic potential after PPARγ ligand treatment were also evaluated. Aerodigestive cancer specimens and normal tissues were evaluated for PPARγ expression on gene expression profiling and immunoblotting. Functional activation of PPARγ reporter gene constructs and increases in PPARγ protein were confirmed in the nuclear compartment after PPARγ ligand treatment. Significant decreases in cell proliferation and clonogenic potential resulted from treatment. Lipid accumulation was induced by PPARγ activator treatment. 75% of tumor specimens and 100% of normal control tissues expressed PPARγ RNA, and PPARγ protein was confirmed in 66% of tumor specimens analyzed by immunoblotting. We conclude PPARγ can be functionally activated in upper aerodigestive cancer and that its activation downregulates several features of the neoplastic phenotype. PPARγ expression in human upper aerodigestive tract tumors and normal cells potentially legitimizes it as a novel intervention target in this disease.

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“…Moreover, we observed that GW9662 (a selective PPARγ antagonist) dramatically inhibited the PGD 2 -and 15d-PGJ 2 -induced increase in Islet-1 expression in differentiated NSC-34 cells. Treatment with 15d-PGJ 2 , retinoic acid, and ciglitazone (a selective PPARγ agonist) suppressed Islet-1 gene expression in neural stem cells generated by culturing dissociated brain cells from newborn mice [53]. In contrast, ciglitazone induced Islet-1 gene expression in human brain tumor stem cell cultures [54].…”

Section: Discussionmentioning

confidence: 99%

The Molecular Mechanisms Underlying Prostaglandin D2-Induced Neuritogenesis in Motor Neuron-Like NSC-34 Cells

Nango

Kosuge

Yoshimura

et al. 2020

Cells

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Prostaglandins are a group of physiologically active lipid compounds derived from arachidonic acid. Our previous study has found that prostaglandin E2 promotes neurite outgrowth in NSC-34 cells, which are a model for motor neuron development. However, the effects of other prostaglandins on neuronal differentiation are poorly understood. The present study investigated the effect of prostaglandin D2 (PGD2) on neuritogenesis in NSC-34 cells. Exposure to PGD2 resulted in increased percentages of neurite-bearing cells and neurite length. Although D-prostanoid receptor (DP) 1 and DP2 were dominantly expressed in the cells, BW245C (a DP1 agonist) and 15(R)-15-methyl PGD2 (a DP2 agonist) had no effect on neurite outgrowth. Enzyme-linked immunosorbent assay demonstrated that PGD2 was converted to 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) under cell-free conditions. Exogenously applied 15d-PGJ2 mimicked the effect of PGD2 on neurite outgrowth. GW9662, a peroxisome proliferator-activated receptor–gamma (PPARγ) antagonist, suppressed PGD2-induced neurite outgrowth. Moreover, PGD2 and 15d-PGJ2 increased the protein expression of Islet-1 (the earliest marker of developing motor neurons), and these increases were suppressed by co-treatment with GW9662. These results suggest that PGD2 induces neuritogenesis in NSC-34 cells and that PGD2-induced neurite outgrowth was mediated by the activation of PPARγ through the metabolite 15d-PGJ2.

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PPARγ Agonists Promote Oligodendrocyte Differentiation of Neural Stem Cells by Modulating Stemness and Differentiation Genes

Cited by 59 publications

References 71 publications

Biological Rationale for the Use of PPARÎ³ Agonists in Glioblastoma

Biological Rationale for the Use of PPARÎ³ Agonists in Glioblastoma

Functional activation of PPARγ in human upper aerodigestive cancer cell lines

The Molecular Mechanisms Underlying Prostaglandin D2-Induced Neuritogenesis in Motor Neuron-Like NSC-34 Cells

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