Cell death is induced by ciglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, independently of PPARγ in human glioma cells

Lee, Myoung Woo; Kim, Dae Seong; Kim, Hye Ryung; Kim, Hye Jin; Yang, Jin Mo; Ryu, Somi; Noh, Young; Lee, Soo Hyun; Son, Meong Hi; Jung, Hye Lim; Yoo, Keon Hee; Koo, Hong Hoe; Sung, Ki Woong

doi:10.1016/j.bbrc.2011.12.001

Cited by 19 publications

(16 citation statements)

References 22 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: 79%

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: 79%

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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“…We also emphasize that interventions that are associated with decreasing mitochondrial function also appear to confer resistance to ischemic injury [11, 32], which is a similar paradigm to our thoughts about using NL-1 to increase stem cell survival. We would be remiss in not mentioning that PPARγ antagonists can have broad effects on critical cell signaling pathways, e.g., Akt activity [16], which could affect the actions of NL-1 in a manner independent of mitoNEET.…”

Section: Discussionmentioning

confidence: 99%

Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress

et al. 2015

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Ischemic heart disease (IHD) is a leading cause of death worldwide, and regenerative therapies through exogenous stem cell delivery hold promising potential. One limitation of such therapies is the vulnerability of stem cells to the oxidative environment associated with IHD. Accordingly, manipulation of stem cell mitochondrial metabolism may be an effective strategy to improve survival of stem cells under oxidative stress. MitoNEET is a redox-sensitive, mitochondrial target of thiazolidinediones (TZDs), and influences cellular oxidative capacity. Pharmacological targeting of mitoNEET with the novel TZD, mitoNEET Ligand-1 (NL-1), improved cardiac stem cell (CSC) survival compared to vehicle (0.1 % DMSO) during in vitro oxidative stress (H2O2). 10 μM NL-1 also reduced CSC maximal oxygen consumption rate (OCR) compared to vehicle. Following treatment with dexamethasone, CSC maximal OCR increased compared to baseline, but NL-1 prevented this effect. Smooth muscle α-actin expression increased significantly in CSC following differentiation compared to baseline, irrespective of NL-1 treatment. When CSCs were treated with glucose oxidase for 7 days, NL-1 significantly improved cell survival compared to vehicle (trypan blue exclusion). NL-1 treatment of cells isolated from mitoNEET knockout mice did not increase CSC survival with H2O2 treatment. Following intramyocardial injection of CSCs into Zucker obese fatty rats, NL-1 significantly improved CSC survival after 24 h, but not after 10 days. These data suggest that pharmacological targeting of mitoNEET with TZDs may acutely protect stem cells following transplantation into an oxidative environment. Continued treatment or manipulation of mitochondrial metabolism may be necessary to produce long-term benefits related to stem cell therapies.

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“…PPAR γ ligands such as thiazolidinedione and rosiglitazone induce differentiation and apoptosis in various human glioblastoma cells [6–11]. For instance, Kato et al showed that 95% of glioma tissue expressed PPAR γ mRNA and that a PPAR γ ligand, troglitazone, inhibited growth in both SK-MG-1 and NB-1 cell lines [5].…”

Section: Introductionmentioning

confidence: 99%

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

2017

BioMed Research International

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PPARγ is a nuclear receptor that regulates differentiation and proliferation and is highly expressed in many cancer cells. Its synthetic ligands, such as rosiglitazone and ciglitazone, and its inhibitor GW9662, were shown to induce cellular differentiation, inhibit proliferation, and lead to apoptosis. Glioblastoma is a common brain tumor with poor survival prospects. Recently, glioblastoma stem cells (GSCs) have been examined as a potential target for anticancer therapy; however, little is known about the combined effect of various agents on GSCs. In this study, we found that cotreatment with PPARγ ligands and GW9662 inhibited stem-like properties in GSC-like spheres, which significantly express SOX2. In addition, this treatment decreased the activation of STAT3 and AKT and decreased the amounts of 14-3-3 gamma and BIS proteins. Moreover, combined administration of small-interfering RNA (siRNA) transfection with PPARγ ligands induced downregulation of SOX2 and MMP2 activity together with inhibition of sphere-forming activity regardless of poly(ADP-ribose) polymerase (PARP) cleavage. Taken together, our findings suggest that a combination therapy using PPARγ ligands and its inhibitor could be a potential therapeutic strategy targeting GSCs.

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Cell death is induced by ciglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, independently of PPARγ in human glioma cells

Cited by 19 publications

References 22 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

Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress

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

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