Knockdown of the TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Sensitizes Glioma Cells to Hypoxia, Irradiation and Temozolomide

The TP53-induced glycolysis and apoptosis regulator (TIGAR) has been shown to decrease glycolysis, to activate the pentose phosphate pathway, and to provide protection against oxidative damage. Hypoxic regions are considered characteristic of glioblastoma and linked with resistance to current treatment strategies. Here, we established that LNT-229 glioma cell lines stably expressed shRNA constructs targeting TIGAR, and exposed them to hypoxia, irradiation and temozolomide. The disruption of TIGAR enhanced levels of reactive oxygen species and cell death under hypoxic conditions, as well as the effectiveness of irradiation and temozolomide. In addition, TIGAR was upregulated by HIF-1α. As a component of a complex network, TIGAR contributes to the metabolic adjustments that arise from either spontaneous or therapy-induced changes in tumor microenvironment.

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Blockage of Potassium Channel Inhibits Proliferation of Glioma Cells Via Increasing Reactive Oxygen Species

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504014x14098532393518 ◽

2014 ◽

Vol 22 (1) ◽

pp. 57-65 ◽

Cited By ~ 1

Author(s):

Li Hu ◽

Li-Li Li ◽

Zhi-Guo Lin ◽

Zhi-Chao Jiang ◽

Hong-Xing Li ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Cycle ◽

Glioma Cell ◽

Glioma Cells ◽

Reactive Oxygen ◽

Dependent Manner ◽

Oxygen Species ◽

Brain Glioma ◽

Protein Levels ◽

Glioma Cell Proliferation

The potassium (K+) channel plays an important role in the cell cycle and proliferation of tumor cells, while its role in brain glioma cells and the signaling pathways remains unclear. We used tetraethylammonium (TEA), a nonselective antagonist of big conductance K+ channels, to block K+ channels in glioma cells, and antioxidant N-acetyl-l-cysteine (NAC) to inhibit production of intracellular reactive oxygen species (ROS). TEA showed an antiproliferation effect on C6 and U87 glioma cells in a time-dependent manner, which was accompanied by an increased intracellular ROS level. Antioxidant NAC pretreatment reversed TEA-mediated antiproliferation and restored ROS level. TEA treatment also caused significant increases in mRNA and protein levels of tumor-suppressor proteins p53 and p21, and the upregulation was attenuated by pretreatment of NAC. Our results suggest that K+ channel activity significantly contributes to brain glioma cell proliferation via increasing ROS, and it might be an upstream factor triggering the activation of the p53/p21Cip1-dependent signaling pathway, consequently leading to glioma cell cycle arrest.

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Oxidation-induced changes in human lens epithelial cells 2. Mitochondria and the generation of reactive oxygen species

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2006.05.023 ◽

2006 ◽

Vol 41 (6) ◽

pp. 926-936 ◽

Cited By ~ 27

Author(s):

Li Huang ◽

Daxin Tang ◽

Marta C. Yappert ◽

Douglas Borchman

Keyword(s):

Reactive Oxygen Species ◽

Epithelial Cells ◽

Reactive Oxygen ◽

Human Lens ◽

Lens Epithelial Cells ◽

Oxygen Species ◽

Human Lens Epithelial Cells ◽

Induced Changes

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Role of NADPH Oxidase-Mediated Reactive Oxygen Species in Podocyte Injury

BioMed Research International ◽

10.1155/2013/839761 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 47

Author(s):

Shan Chen ◽

Xian-Fang Meng ◽

Chun Zhang

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Epithelial To Mesenchymal Transition ◽

Kidney Diseases ◽

Treatment Strategies ◽

Reactive Oxygen ◽

Glomerular Sclerosis ◽

Oxygen Species ◽

Podocyte Injury ◽

Mesenchymal Transition

Proteinuria is an independent risk factor for end-stage renal disease (ESRD) (Shankland, 2006). Recent studies highlighted the mechanisms of podocyte injury and implications for potential treatment strategies in proteinuric kidney diseases (Zhang et al., 2012). Reactive oxygen species (ROS) are cellular signals which are closely associated with the development and progression of glomerular sclerosis. NADPH oxidase is a district enzymatic source of cellular ROS production and prominently expressed in podocytes (Zhang et al., 2010). In the last decade, it has become evident that NADPH oxidase-derived ROS overproduction is a key trigger of podocyte injury, such as renin-angiotensin-aldosterone system activation (Whaley-Connell et al., 2006), epithelial-to-mesenchymal transition (Zhang et al., 2011), and inflammatory priming (Abais et al., 2013). This review focuses on the mechanism of NADPH oxidase-mediated ROS in podocyte injury under different pathophysiological conditions. In addition, we also reviewed the therapeutic perspectives of NADPH oxidase in kidney diseases related to podocyte injury.

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Effect of GDM on the Expression of MT1-MMP and u-PA in Glioma Cells

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.1033-1034.220 ◽

2014 ◽

Vol 1033-1034 ◽

pp. 220-223

Author(s):

Xue Mei Han ◽

Li Bo Wang ◽

Ni Ni Li ◽

Song Yan Liu

Keyword(s):

Normal Control ◽

Glioma Cell ◽

Fetal Bovine Serum ◽

Glioma Cells ◽

Normal Control Group ◽

Control Group ◽

Rt Pcr ◽

Glioma Cell Lines ◽

Fetal Bovine ◽

Identify Gene Expression

To examine the effect of GDM on the expression of MT1-MMP and u-PA genes in glioma cells. Glioma cell lines U251 and U87 were cultured in DMEM medium supplemented with 10% fetal bovine serum. RT-PCR was used to identify gene expression level. The level of u-PA mRNA was up-regulated significantly in the HGF group compared with the normal control group (P<0.05). The expression of MT1-MMP and u-PA was significantly lower in the GDM group than in the normal control and HGF groups (P<0.05). The expression of u-PA in the HGF+GDM group was down-regulated significantly compared with the normal control and HGF groups (P<0.05).GDM can inhibit expression of both MT1-MMP and u-PA in glioma cells.

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Levodopa modulating effects of inducible nitric oxide synthase and reactive oxygen species in glioma cells

Life Sciences ◽

10.1016/s0024-3205(02)02204-x ◽

2002 ◽

Vol 72 (2) ◽

pp. 185-198 ◽

Cited By ~ 28

Author(s):

Mark K Soliman ◽

Elizabeth Mazzio ◽

Karam F.A Soliman

Keyword(s):

Nitric Oxide ◽

Reactive Oxygen Species ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Glioma Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Oxide Synthase ◽

Inducible Nitric Oxide

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The differential role of reactive oxygen species in early and late stages of cancer

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00247.2017 ◽

2017 ◽

Vol 313 (6) ◽

pp. R646-R653 ◽

Cited By ~ 36

Author(s):

Mohamad Assi

Keyword(s):

Reactive Oxygen Species ◽

Tumor Cells ◽

Cancer Progression ◽

Reactive Oxygen ◽

Pentose Phosphate ◽

Oxygen Species ◽

Redox Biology ◽

Oxidative Damages ◽

Late Stages

The large doses of vitamins C and E and β-carotene used to reduce reactive oxygen species (ROS) production and oxidative damages in cancerous tissue have produced disappointing and contradictory results. This therapeutic conundrum was attributed to the double-faced role of ROS, notably, their ability to induce either proliferation or apoptosis of cancer cells. However, for a ROS-inhibitory approach to be effective, it must target ROS when they induce proliferation rather than apoptosis. On the basis of recent advances in redox biology, this review underlined a differential regulation of prooxidant and antioxidant system, respective to the stage of cancer. At early precancerous and neoplastic stages, antioxidant activity decreases and ROS appear to promote cancer initiation via inducing oxidative damage and base pair substitution mutations in prooncogenes and tumor suppressor genes, such as RAS and TP53, respectively. Whereas in late stages of cancer progression, tumor cells escape apoptosis by producing high levels of intracellular antioxidants, like NADPH and GSH, via the pentose phosphate pathway to buffer the excessive production of ROS and related intratumor oxidative injuries. Therefore, antioxidants should be prohibited in patients with advanced stages of cancer and/or undergoing anticancer therapies. Interestingly, the biochemical and biophysical properties of some polyphenols allow them to selectively recognize tumor cells. This characteristic was exploited to design and deliver nanoparticles coated with low doses of polyphenols and containing chemotherapeutic drugs into tumor-bearing animals. First results are encouraging, which may revolutionize the conventional use of antioxidants in cancer.

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Glioma cell antioxidant capacity relative to reactive oxygen species produced by dopamine

Journal of Applied Toxicology ◽

10.1002/jat.954 ◽

2004 ◽

Vol 24 (2) ◽

pp. 99-106 ◽

Cited By ~ 46

Author(s):

Elizabeth A. Mazzio ◽

Karam F. A. Soliman

Keyword(s):

Reactive Oxygen Species ◽

Antioxidant Capacity ◽

Glioma Cell ◽

Reactive Oxygen ◽

Oxygen Species

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LncRNA-XIST interacts with miR-29c to modulate the chemoresistance of glioma cell to TMZ through DNA mismatch repair pathway

Bioscience Reports ◽

10.1042/bsr20170696 ◽

2017 ◽

Vol 37 (5) ◽

Cited By ~ 44

Author(s):

Peng Du ◽

Haiting Zhao ◽

Renjun Peng ◽

Qing Liu ◽

Jian Yuan ◽

...

Keyword(s):

Cell Proliferation ◽

Mismatch Repair ◽

Cell Lines ◽

Glioma Cell ◽

Dna Mismatch Repair ◽

Tumor Biology ◽

Glioma Cells ◽

Dna Mismatch ◽

Cell Proliferation Inhibition ◽

Glioma Cell Lines

Temozolomide (TMZ) is the most commonly used alkylating agent in glioma chemotherapy. However, growing resistance to TMZ remains a major challenge for clinicians. Recent evidence emphasizes the key regulatory roles of non-coding RNAs (lncRNAs and miRNAs) in tumor biology, including the chemoresistance of cancers. However, little is known about the role and regulation mechanisms of lncRNA cancer X-inactive specific transcripts (XIST) in glioma tumorigenesis and chemotherapy resistance. In the present study, higher XIST expression was observed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time. XIST knockdown alone was sufficient to inhibit glioma cell proliferation and to amplify TMZ-induced cell proliferation inhibition. Moreover, XIST knockdown can sensitize TMZ-resistant glioma cells to TMZ. XIST can inhibit miR-29c expression by directly targetting TMZ-resistant glioma cells. DNA repair protein O6-methylguanine-DNA methytransferase (MGMT) plays a key role in TMZ resistance; transcription factor specificity protein 1 (SP1), a regulator of DNA mismatch repair (MMR) key protein MSH6, has been reported to be up-regulated in TMZ-resistant glioma cell lines. In the present study, we show that XIST/miR-29c coregulates SP1 and MGMT expression in TMZ-resistant glioma cell lines. Our data suggest that XIST can amplify the chemoresistance of glioma cell lines to TMZ through directly targetting miR-29c via SP1 and MGMT. XIST/miR-29c may be a potential therapeutic target for glioma treatment.

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Intraperitoneal Triamcinolone Reduces Postoperative Adhesions, Possibly through Alteration of Mitochondrial Function

Journal of Clinical Medicine ◽

10.3390/jcm11020301 ◽

2022 ◽

Vol 11 (2) ◽

pp. 301

Author(s):

Neeraja Purandare ◽

Katherine J. Kramer ◽

Paige Minchella ◽

Sarah Ottum ◽

Christopher Walker ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Mitochondrial Function ◽

Molecular Mechanisms ◽

Human Fibroblasts ◽

Reactive Oxygen ◽

Retrospective Chart Review ◽

Oxygen Species ◽

Abdominal Myomectomy ◽

Hypoxic Conditions

Adhesions frequently occur postoperatively, causing morbidity. In this noninterventional observational cohort study, we enrolled patients who presented for repeat abdominal surgery, after a history of previous abdominal myomectomy, from March 1998 to June 20210 at St. Vincent’s Catholic Medical Centers. The primary outcome of this pilot study was to compare adhesion rates, extent, and severity in patients who were treated with intraperitoneal triamcinolone acetonide during the initial abdominal myomectomy (n = 31) with those who did not receive any antiadhesion interventions (n = 21), as documented on retrospective chart review. Adhesions were blindly scored using a standard scoring system. About 32% of patients were found to have adhesions in the triamcinolone group compared to 71% in the untreated group (p < 0.01). Compared to controls, adhesions were significantly less in number (0.71 vs. 2.09, p < 0.005), severity (0.54 vs. 1.38, p < 0.004), and extent (0.45 vs. 1.28, p < 0.003). To understand the molecular mechanisms, human fibroblasts were incubated in hypoxic conditions and treated with triamcinolone or vehicle. In vitro studies showed that triamcinolone directly prevents the surge of reactive oxygen species triggered by 2% hypoxia and prevents the increase in TGF-β1 that leads to the irreversible conversion of fibroblasts to an adhesion phenotype. Triamcinolone prevents the increase in reactive oxygen species through alterations in mitochondrial function that are HIF-1α-independent. Controlling mitochondrial function may thus allow for adhesion-free surgery and reduced postoperative complications.

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