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; Tovar‐Moll, Fernanda; Souza, Jorge de; Lima, Flávia Regina Souza; Anderluh, Gregor; Moura‐Neto, Vivaldo

doi:10.2174/1568026611212190006

Cited by 6 publications

(6 citation statements)

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“…However, the road from basic to translational research, and from preclinical models to clinical trials, is long. The methods for drug delivery across the blood‐brain barrier still necessitate considerable improvement (Balça‐Silva et al, ; Kahn et al, ; Naumann et al, ).…”

Section: Therapeutic Approaches Focused On Ecm and Invasionmentioning

confidence: 99%

Glioma infiltration and extracellular matrix: key players and modulators

Ferrer

Moura‐Neto

Mentlein

2018

Glia

144

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An outstanding characteristic of gliomas is their infiltration into brain parenchyma, a property that impairs complete surgical resection; consequently, these tumors might recur, resulting in a high mortality rate. Gliomas invade along preferential routes, such as those along white matter tracts and in the perineuronal and perivascular spaces. Brain extracellular components and their partners and modulators play a crucial role in glioma cell invasion. This review presents an extensive survey of the literature, showing how the brain extracellular matrix (ECM) is modulated during the glioma infiltration process. We explore aspects of ECM interaction with glioma cells, reviewing the main glycosaminoglycans, glycoproteins and proteoglycans. We discuss the roles of ECM-binding proteins, including CD44, RHAMM, integrins and axonal guidance molecules, and highlight the role of proteases and glycosidases in glioma infiltration; in binding and release chemokines, cytokines and growth factors; and in generating new bioactive ECM fragments. We also consider the roles of cytoskeletal signaling, angiogenesis, miRNAs and the glial-to-mesenchymal transition linked to glioma invasion. We closely discuss therapeutic approaches based on the modulation of the extracellular matrix, targeting the control of glioma infiltration, its relative failure in clinical trials, and potential means to overcome this difficulty.

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Section: Therapeutic Approaches Focused On Ecm and Invasionmentioning

confidence: 99%

Glioma infiltration and extracellular matrix: key players and modulators

Ferrer

Moura‐Neto

Mentlein

2018

Glia

144

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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: Biological Usementioning

confidence: 99%

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

Frangež¹,

Šuput²,

Molgó³

et al. 2017

Preprint

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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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“…Despite the fact that low concentrations of EqTs are lethal, several studies have been reported on their effects on cancer cells [56][57][58]. Furthermore, they have been tested as immunotoxins targeting at Giardia duodenalis [59].…”

Section: Biological Usementioning

confidence: 99%

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

Frangež¹,

Šuput²,

Molgó³

et al. 2017

Preprint

View full text Add to dashboard Cite

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 equine, 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 6 publications

References 0 publications

Glioma infiltration and extracellular matrix: key players and modulators

Glioma infiltration and extracellular matrix: key players and modulators

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

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

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