Dobesilate inhibits the activation of signal transducer and activator of transcription 3, and the expression of cyclin D1 and bcl-XL in glioma cells

Cuevas, Pedro; Díaz-González, Diana; Sánchez, Israel M.; Lozano, Rosa M.; Giménez‐Gallego, Guillermo; Dujovny, Manuel

doi:10.1179/016164106x97982

Cited by 19 publications

(14 citation statements)

References 18 publications

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“…The death receptor and mitochondrial death pathways may be linked by Bcl-XL, which subsequently activates the proteolytic activation of effector caspases-3 to trigger the mitochondrial dysfunction and cytochrome c release [17][18][19]. Also, DEX pre-treatment has been recently reported to interfere with apoptotic death in brain tumour cells by the transcriptional activation of a Bcl-XL gene [20][21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

The effects of dexamethasone on the proliferation and apoptosis of human ovarian cancer cells induced by paclitaxel

Hou

Guan

et al. 2014

Journal of Ovarian Research

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Background: Dexamethasone (DEX) has been routinely used as a pre-treatment in the clinical application of paclitaxel (PTX) to treat ovarian cancer. However, PTX-induced apoptosis might be inhibited by DEX. This study was undertaken to investigate the effects of DEX on the apoptosis induced by PTX. Methods: Both of SKOV-3 and HO-8910 human ovarian cancer cells were divided into four groups: (1) untreated (Con); (2) treated with DEX (0.1 μM) alone; (3) treated with PTX (50 nM); and (4) pre-treated with DEX (0.1 μM), and 24 h later, treated with PTX (DEX + PTX). Cell proliferation was determined by the 3-(4,5)-dimethylthiahiazo (−z-y1)-3,5-di-phenytetrazoliumromide (MTT) dye uptake method, while cell apoptosis was analyzed by propidium iodide (PI) staining and flow cytometry. Then, reverse transcription polymerase chain reactions (RT-PCRs) were applied to semi-quantitative analysis, followed by western blot analysis. Statistical analysis was performed, with Fisher's least significant difference test.

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Section: Introductionmentioning

confidence: 99%

The effects of dexamethasone on the proliferation and apoptosis of human ovarian cancer cells induced by paclitaxel

Hou

Guan

et al. 2014

Journal of Ovarian Research

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“…Furthermore, Gu et al used higher concentration (50 vs. 15 nM) of the decoys, more prolonged (24 vs. 4 h) lipofectamine-mediated transfection, and a different control decoy (scrambled vs. mutated), which could also contribute to the differences in the results. Cuevas et al [2006b] reported that dobesilate-a synthetic FGF inhibitor-reduces the level of Stat3 phosphorylation in C6 glioma cells, with a concurrent reduction in expression of Bcl2l1 and Ccnd1 assessed by immunocytochemistry. These results appear contradictory to our results suggesting that Stat1, and not Stat3, maintains the expression of Bcl2l1 in the C6 glioma cells.…”

Section: Discussionmentioning

confidence: 98%

Signal transducer and activator of transcription 1 (Stat1) maintains basal mRNA expression of pro-survival stat3-target genes in glioma C6 cells

et al. 2011

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The STAT proteins (signal transducers and activators of transcription) are transcription factors mediating cytokine/growth factor signaling, which play important role in controlling cell cycle progression and apoptosis. In many cancer cell lines and tumors (including gliomas) the STAT proteins (in particular Stats 1, 3, and 5) are persistently activated. In this study, we employed DNA decoys, siRNAs, and protein overexpression, to elucidate the role of Stat1 and Stat3 in regulation of expression of endogenous Stat3-target genes (Bcl2l1, Myc, Ccnd1) and a Stat-driven reporter plasmid, in rat C6 glioma cells. The results obtained with the decoys and siRNA suggest that in proliferating C6 cells, Stat1 supports the basal expression of Bcl2l1, while the decoy and chromatin immunoprecipitation results suggest it also plays a similar role for Myc. In the Stat-driven reporter system, overexpression of Stat1 stimulated, while overexpression of Stat3 inhibited the reporter gene expression. The level of Stat1 phosphorylation observed under basal conditions in proliferating glioma C6 cells is very low. Therefore, we speculate that it is the activity of the unphosphorylated Stat1 that is inhibited by Stat1 decoy or Stat1 siRNA. Taken together, our results demonstrate that it is Stat1 not Stat3 that maintains the expression of Bcl2l1 and possibly Myc in proliferating glioma C6 cells. An established paradigm is that Stat3 exerts a pro-survival and potentially oncogenic effects, while Stat1 is mainly associated with the immune response. Our results add to a number of reports that challenge this paradigm.

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“…Treatment of C6 glioma cells with dobesilate in vitro triggered apoptosis and growth arrest (80). Further studies in glioma cells showed that dobesilate significantly inhibited constitutive expression of tyrosine phosphorylated STAT-3 (81), activation of the MAPK extracellular signal-regulated protein kinases 1/2 (82), and expression of the prosurvival proteins Bcl-xL and cyclin D1 (81). These results support the idea that dobesilate increased apoptosis and decreased cell growth and survival in part by blocking STAT-3 activation.…”

Section: Inhibition Of Upstream Kinasesmentioning

confidence: 99%

Signal Transducer and Activator of Transcription-3: A Molecular Hub for Signaling Pathways in Gliomas

Brantley

Benveniste

2008

Molecular Cancer Research

210

159

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Dobesilate inhibits the activation of signal transducer and activator of transcription 3, and the expression of cyclin D1 and bcl-XL in glioma cells

Cited by 19 publications

References 18 publications

The effects of dexamethasone on the proliferation and apoptosis of human ovarian cancer cells induced by paclitaxel

The effects of dexamethasone on the proliferation and apoptosis of human ovarian cancer cells induced by paclitaxel

Signal transducer and activator of transcription 1 (Stat1) maintains basal mRNA expression of pro-survival stat3-target genes in glioma C6 cells

Signal Transducer and Activator of Transcription-3: A Molecular Hub for Signaling Pathways in Gliomas

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