Combination Treatment with PPAR<i>γ</i>Ligand and Its Specific Inhibitor GW9662 Downregulates BIS and 14-3-3 Gamma, Inhibiting Stem-Like Properties in Glioblastoma Cells

Im, Chang‐Nim

doi:10.1155/2017/5832824

Cited by 12 publications

(8 citation statements)

References 44 publications

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“…31 Recent studies have revealed that GW9662, with or without PPARγ ligands, could be a potential therapeutic strategy targeting glioblastoma stem cells. 55,56 In accordance with the knockdown assays, our results revealed that GW9662 could inhibit the proliferation of BCa 5637, T24 and UM-UC-3 cells in a time and dose-dependent manner. The invasion and migration rate were also reduced in BCa cells treated with GW9662, with reversed EMT markers, which could suggest tumour malignancy.…”

Section: Discussionsupporting

confidence: 77%

PPARγ inhibition regulates the cell cycle, proliferation and motility of bladder cancer cells

Cheng

Qian

Wang

et al. 2019

J Cellular Molecular Medi

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Peroxisome proliferator‐activated receptor gamma (PPARγ) is a member of the nuclear receptor family of ligand‐activated transcription factors and plays an important role in regulating cell proliferation, inflammation and lipid and glucose homeostasis. Our results revealed that PPARγ was up‐regulated in human bladder cancer (BCa) tissues both at transcriptional and translational levels. Moreover, down‐regulation of PPARγ mRNA or inhibition of PPARγ function (using GW9662, antagonist of PPARγ) could significantly suppress the proliferation of BCa cells. Furthermore, the cell cycle arrested in G0/G1 phase was also induced by the down‐regulated PPARγ possibly through AKT‐mediated up‐regulation of p21/p27, whereas no significant transformation of apoptosis was observed. In addition, knockdown or inhibition of PPARγ might reduce the invasion and migration of BCa cells by affecting epithelial‐mesenchymal transition‐related proteins through AKT/GSK3β signalling pathway. Additionally, in vivo studies showed that BCa cell proliferation was significantly suppressed by GW9662. In conclusion, our results indicated that PPARγ might be crucial for BCa tumorigenesis by interfering with the motility and viability of BCa cells.

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Section: Discussionsupporting

confidence: 77%

PPARγ inhibition regulates the cell cycle, proliferation and motility of bladder cancer cells

Cheng

Qian

Wang

et al. 2019

J Cellular Molecular Medi

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“…Overexpression of PPARγ is also a hallmark of GBM cells [33] and it has been documented that the PPARγ agonists thiazolidinediones and Fmoc-L-Leucine inhibit growth, proliferation, and induce apoptosis in various human glioblastoma cells in vivo, and thus may be regarded as a potential agents for GBM therapy [34,35,36,37,38,39]. The obvious conclusion is to combine both factors to potentiate anti-glioma effects [31].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Biotinylated PAMAM G3 Dendrimers Conjugated with COX-2 Inhibitor (celecoxib) and PPARγ Agonist (Fmoc-L-Leucine) on Human Normal Fibroblasts, Immortalized Keratinocytes and Glioma Cells in Vitro

et al. 2019

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Glioblastoma multiforme (GBM) is the most malignant type of central nervous system tumor that is resistant to all currently used forms of therapy. Thus, more effective GBM treatment strategies are being investigated, including combined therapies with drugs that may cross the blood brain barrier (BBB). Another important issue considers the decrease of deleterious side effects of therapy. It has been shown that nanocarrier conjugates with biotin can penetrate BBB. In this study, biotinylated PAMAM G3 dendrimers substituted with the recognized anticancer agents cyclooxygenase-2 (COX-2) inhibitor celecoxib and peroxisome proliferator-activated receptor γ (PPARγ) agonist Fmoc-L-Leucine (G3-BCL) were tested in vitro on human cell lines with different p53 status: glioblastoma (U-118 MG), normal fibroblasts (BJ) and immortalized keratinocytes (HaCaT). G3-BCL penetrated efficiently into the lysosomal and mitochondrial compartments of U-118 MG cells and induced death of U-118 MG cells via apoptosis and inhibited proliferation and migration at low IC50 = 1.25 µM concentration, considerably lower than either drug applied alone. Comparison of the effects of G3-BCL on expression of COX-2 and PPARγ protein and PGE2 production of three different investigated cell line phenotypes revealed that the anti-glioma effect of the conjugate was realized by other mechanisms other than influencing PPAR-γ expression and regardless of p53 cell status, it was dependent on COX-2 protein level and high PGE2 production. Similar G3-BCL cytotoxicity was seen in normal fibroblasts (IC50 = 1.29 µM) and higher resistance in HaCaT cells (IC50 = 4.49 µM). Thus, G3-BCL might be a good candidate for the targeted, local glioma therapy with limited site effects.

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“…17 Higher levels of 14-3-3 are also evident in GSC. 18 As indicated above, both miR-7 and miR-451 can repress 14-3-3ζ in both tumour and nonneoplastic cells. 8,14,19 The loss of 14-3-3 sensitizes GBM/GSC to apoptosis as well as preventing NAS synthesis, thereby preventing any trophic effects of NAS via the TrkB.…”

Section: -3-3mentioning

confidence: 85%

Glioblastoma: Role of Mitochondria N-acetylserotonin/Melatonin Ratio in Mediating Effects of miR-451 and Aryl Hydrocarbon Receptor and in Coordinating Wider Biochemical Changes

Anderson¹,

Reiter

2019

Int J�Tryptophan�Res

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A wide array of different factors and processes have been linked to the biochemical underpinnings of glioblastoma multiforme (GBM) and glioblastoma stem cells (GSC), with no clear framework in which these may be integrated. Consequently, treatment of GBM/GSC is generally regarded as very poor. This article provides a framework that is based on alterations in the regulation of the melatonergic pathways within mitochondria of GBM/GSC. It is proposed that the presence of high levels of mitochondria-synthesized melatonin is toxic to GBM/GSC, with a number of processes in GBM/GSC acting to limit melatonin’s synthesis in mitochondria. One such factor is the aryl hydrocarbon receptor, which increases cytochrome P450 (CYP)1b1 in mitochondria, leading to the ‘backward’ conversion of melatonin to N -acetylserotonin (NAS). N -acetylserotonin has some similar, but some important differential effects compared with melatonin, including its activation of the tyrosine receptor kinase B (TrkB) receptor. TrkB activation is important to GBM/GSC survival and proliferation. A plethora of significant, but previously disparate, data on GBM/GSC can then be integrated within this framework, including miR-451, AMP-activated protein kinase (AMPK)/mTOR, 14-3-3 proteins, sirtuins, tryptophan 2,3-dioxygenase, and the kynurenine pathways. Such a conceptualization provides a framework for the development of more effective treatment for this poorly managed condition.

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Combination Treatment with PPARγLigand and Its Specific Inhibitor GW9662 Downregulates BIS and 14-3-3 Gamma, Inhibiting Stem-Like Properties in Glioblastoma Cells

Cited by 12 publications

References 44 publications

PPARγ inhibition regulates the cell cycle, proliferation and motility of bladder cancer cells

PPARγ inhibition regulates the cell cycle, proliferation and motility of bladder cancer cells

The Effect of Biotinylated PAMAM G3 Dendrimers Conjugated with COX-2 Inhibitor (celecoxib) and PPARγ Agonist (Fmoc-L-Leucine) on Human Normal Fibroblasts, Immortalized Keratinocytes and Glioma Cells in Vitro

Glioblastoma: Role of Mitochondria N-acetylserotonin/Melatonin Ratio in Mediating Effects of miR-451 and Aryl Hydrocarbon Receptor and in Coordinating Wider Biochemical Changes

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