Equinatoxin II Potentiates Temozolomide- and Etoposide-Induced Glioblastoma Cell Death

Kahn, Suzana Assad; Biasoli, Deborah; García, Celina; Geraldo, Luiz Henrique Medeiros; Pontes, Bruno; Sobrinho, Morgana; Frauches, Ana Carina Bon; Romão, Luciana; Soletti, Rossana C.; Assuncao, Fernando dos Santos; Tovar‐Moll, Fernanda; Souza, Jorge Marcondes de; Lima, Flávia Regina Souza; Anderluh, Gregor; Moura‐Neto, Vivaldo

doi:10.2174/156802612804910250

Cited by 21 publications

(21 citation statements)

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“…7 GBM cells are radio- and chemo-resistant; therefore, ways to increase cell death are one of the major targets in GBM research. 8, 9, 10 Moreover, the parenchymal infiltration of GBM cells makes total surgical resection an impossible task, 11 rendering the study of tumor invasion mechanisms an issue regarding GBM therapy, besides the study of survival mechanisms of GBM cells. 7 …”

Section: Introductionmentioning

confidence: 99%

Glioblastoma cells inhibit astrocytic p53-expression favoring cancer malignancy

et al. 2014

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The tumor microenvironment has a dynamic and usually cancer-promoting function during all tumorigenic steps. Glioblastoma (GBM) is a fatal tumor of the central nervous system, in which a substantial number of non-tumoral infiltrated cells can be found. Astrocytes neighboring these tumor cells have a particular reactive phenotype and can enhance GBM malignancy by inducing aberrant cell proliferation and invasion. The tumor suppressor p53 has a potential non-cell autonomous function by modulating the expression of secreted proteins that influence neighbor cells. In this work, we investigated the role of p53 on the crosstalk between GBM cells and astrocytes. We show that extracellular matrix (ECM) from p53+/− astrocytes is richer in laminin and fibronectin, compared with ECM from p53+/+ astrocytes. In addition, ECM from p53+/− astrocytes increases the survival and the expression of mesenchymal markers in GBM cells, which suggests haploinsufficient phenotype of the p53+/– microenvironment. Importantly, conditioned medium from GBM cells blocks the expression of p53 in p53+/+ astrocytes, even when DNA was damaged. These results suggest that GBM cells create a dysfunctional microenvironment based on the impairment of p53 expression that in turns exacerbates tumor endurance.

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Section: Introductionmentioning

confidence: 99%

Glioblastoma cells inhibit astrocytic p53-expression favoring cancer malignancy

et al. 2014

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“…The human tumor cell lines, GBM02 and GBM11 cells, were established and characterized in our laboratory and maintained directly in DMEM/F12 supplemented with bovine serum after being collected from a GBM patient biopsy sample, as previously described [28], [29]. The human cell line OB1 was established and characterized by the laboratory of Dr. Hervé Chneiweiss and maintained in NS34 serum-free medium as described by Thirant et al (2012).…”

Section: Methodsmentioning

confidence: 99%

“…The SOX2, OCT-4A, NANOG, Cx43, Cx46, and Slug proteins were analyzed by Western blotting as originally described by Towbin and adapted by Balça-Silva and Kahn in both the GBM and GBM-SF cell lines [28], [32], [33]. Briefly, cells were centrifuged at 500× g for 10 minutes at 4°C.…”

Section: Methodsmentioning

confidence: 99%

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The Expression of Connexins and SOX2 Reflects the Plasticity of Glioma Stem-Like Cells

Balça-Silva

Matias

Dubois

et al. 2017

Translational Oncology

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Glioblastoma (GBM) is the most malignant primary brain tumor, with an average survival rate of 15 months. GBM is highly refractory to therapy, and such unresponsiveness is due, primarily, but not exclusively, to the glioma stem-like cells (GSCs). This subpopulation express stem-like cell markers and is responsible for the heterogeneity of GBM, generating multiple differentiated cell phenotypes. However, how GBMs maintain the balance between stem and non-stem populations is still poorly understood. We investigated the GBM ability to interconvert between stem and non-stem states through the evaluation of the expression of specific stem cell markers as well as cell communication proteins. We evaluated the molecular and phenotypic characteristics of GSCs derived from differentiated GBM cell lines by comparing their stem-like cell properties and expression of connexins. We showed that non-GSCs as well as GSCs can undergo successive cycles of gain and loss of stem properties, demonstrating a bidirectional cellular plasticity model that is accompanied by changes on connexins expression. Our findings indicate that the interconversion between non-GSCs and GSCs can be modulated by extracellular factors culminating on differential expression of stem-like cell markers and cell-cell communication proteins. Ultimately, we observed that stem markers are mostly expressed on GBMs rather than on low-grade astrocytomas, suggesting that the presence of GSCs is a feature of high-grade gliomas. Together, our data demonstrate the utmost importance of the understanding of stem cell plasticity properties in a way to a step closer to new strategic approaches to potentially eliminate GSCs and, hopefully, prevent tumor recurrence.

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“…Despite the fact that low concentrations of EqTs are lethal, several studies have been reported on their effects on cancer cells [65,66,67]. Furthermore, they have been tested as the toxic moiety of immunotoxins targeting at Giardia duodenalis [68].…”

Section: Equinatoxinsmentioning

confidence: 99%

Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins

Frangež

Šuput

Molgó

et al. 2017

Toxins

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Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

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Equinatoxin II Potentiates Temozolomide- and Etoposide-Induced Glioblastoma Cell Death

Cited by 21 publications

References 0 publications

Glioblastoma cells inhibit astrocytic p53-expression favoring cancer malignancy

Glioblastoma cells inhibit astrocytic p53-expression favoring cancer malignancy

The Expression of Connexins and SOX2 Reflects the Plasticity of Glioma Stem-Like Cells

Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins

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