Abstract
Glioblastoma (GBM) is considered incurable due to its resistance to current cancer treatments. So far, all clinically available alternatives for treating GBM are limited, evoking the development of novel treatment strategies that can more effectively manage these tumors. Extensive effort is being dedicated to characterize the molecular basis of GBM resistance to chemotherapy and to explore novel therapeutic procedures that may improve overall survival. Cytolysins are toxins that form pores in target cell membranes, modifying ion homeostasis and leading to cell death. These pore-forming toxins might be used, therefore, to enhance the efficiency of conventional chemotherapeutic drugs, facilitating their entrance into the cell. In this study, we show that a non-cytotoxic concentration of equinatoxin II (EqTx-II), a pore-forming toxin from the sea anemone Actinia equina, potentiates the cytotoxicity induced by temozolomide (TMZ), a first-line GBM treatment, and by etoposide (VP-16), a second- or third-line GBM treatment. We also suggest that this effect is selective to GBM cells and occurs via PI3K/Akt pathway inhibition. Finally, Magnetic resonance imaging (MRI) revealed that a non-cytotoxic concentration of EqTx-II potentiates the VP-16-induced inhibition of GBM growth in vivo. These combined therapies constitute a new and potentially valuable tool for GBM treatment, leading to the requirement of lower concentrations of chemotherapeutic drugs and possibly reducing, therefore, the adverse effects of chemotherapy.
Keywords: glioblastoma, equinatoxin II, temozolomide, etoposide, chemotherapeutic drugs, novel treatment strategies, Cytolysins, novel therapeutic procedures, chemotherapy, cell death, Actinia equina.
Current Topics in Medicinal Chemistry
Title:Equinatoxin II Potentiates Temozolomide- and Etoposide-Induced Glioblastoma Cell Death
Volume: 12 Issue: 19
Author(s): Suzana Assad Kahn, Deborah Biasoli, Celina Garcia, Luiz Henrique M. Geraldo, Bruno Pontes, Morgana Sobrinho, Ana Carina Bon Frauches, Luciana Romao, Rossana C. Soletti, Fernando dos Santos Assuncao, Fernanda Tovar-Moll, Jorge Marcondes de Souza, Flavia R.S. Lima, Gregor Anderluh and Vivaldo Moura-Neto
Affiliation:
Keywords: glioblastoma, equinatoxin II, temozolomide, etoposide, chemotherapeutic drugs, novel treatment strategies, Cytolysins, novel therapeutic procedures, chemotherapy, cell death, Actinia equina.
Abstract: Glioblastoma (GBM) is considered incurable due to its resistance to current cancer treatments. So far, all clinically available alternatives for treating GBM are limited, evoking the development of novel treatment strategies that can more effectively manage these tumors. Extensive effort is being dedicated to characterize the molecular basis of GBM resistance to chemotherapy and to explore novel therapeutic procedures that may improve overall survival. Cytolysins are toxins that form pores in target cell membranes, modifying ion homeostasis and leading to cell death. These pore-forming toxins might be used, therefore, to enhance the efficiency of conventional chemotherapeutic drugs, facilitating their entrance into the cell. In this study, we show that a non-cytotoxic concentration of equinatoxin II (EqTx-II), a pore-forming toxin from the sea anemone Actinia equina, potentiates the cytotoxicity induced by temozolomide (TMZ), a first-line GBM treatment, and by etoposide (VP-16), a second- or third-line GBM treatment. We also suggest that this effect is selective to GBM cells and occurs via PI3K/Akt pathway inhibition. Finally, Magnetic resonance imaging (MRI) revealed that a non-cytotoxic concentration of EqTx-II potentiates the VP-16-induced inhibition of GBM growth in vivo. These combined therapies constitute a new and potentially valuable tool for GBM treatment, leading to the requirement of lower concentrations of chemotherapeutic drugs and possibly reducing, therefore, the adverse effects of chemotherapy.
Export Options
About this article
Cite this article as:
Kahn Assad Suzana, Biasoli Deborah, Garcia Celina, Geraldo Henrique M. Luiz, Pontes Bruno, Sobrinho Morgana, Frauches Carina Bon Ana, Romao Luciana, Soletti C. Rossana, Assuncao dos Santos Fernando, Tovar-Moll Fernanda, de Souza Marcondes Jorge, Lima R.S. Flavia, Anderluh Gregor and Moura-Neto Vivaldo, Equinatoxin II Potentiates Temozolomide- and Etoposide-Induced Glioblastoma Cell Death, Current Topics in Medicinal Chemistry 2012; 12 (19) . https://dx.doi.org/10.2174/1568026611212190006
DOI https://dx.doi.org/10.2174/1568026611212190006 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Serotonergic and Cholinergic Strategies as Potential Targets for the Treatment of Schizophrenia
Current Pharmaceutical Design Emerging Features in the Regulation of MMP-9 Gene Expression for the Development of Novel Molecular Targets and Therapeutic Strategies
Current Drug Targets - Inflammation & Allergy Targeting Opioid and Neurokinin-1 Receptors to Treat Alcoholism
Current Medicinal Chemistry Mesenchymal Stem Cells in Cartilage Repair: State of the Art and Methods to monitor Cell Growth, Differentiation and Cartilage Regeneration
Current Medicinal Chemistry β-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection
Current HIV Research Glutamate Receptor Agonists: Stereochemical Aspects
Current Topics in Medicinal Chemistry MicroRNAs in Cancer Therapy: From Bench to Bedside
Current Cancer Therapy Reviews dUTPase in Human Neoplastic Cells as a Potential Target for Therapeutic Intervention
Current Protein & Peptide Science Nanotechnology Platforms; An Innovative Approach to Brain Tumor Therapy
Medicinal Chemistry State-of-the-Art Magnetic Resonance Spectroscopy in Oncologic Imaging
Current Molecular Imaging (Discontinued) Protein Kinase C and Oxidative Stress in an Animal Model of Mania
Current Neurovascular Research MicroRNAs as Diagnostic, Prognostic and Predictive Biomarkers of Cardiac Disease
Recent Patents on Biomarkers Potential Therapeutic Application of Chondroitin Sulfate/Dermatan Sulfate
Current Drug Discovery Technologies Chitinases: Biomarkers for Human Diseases
Protein & Peptide Letters Infringement of the Barriers of Cancer Via Dietary Phytoconstituents Capsaicin Through Novel Drug Delivery System
Current Drug Delivery Meet Our Editorial Board Member
Current Neuropharmacology In Situ Gene Therapy for Prostate Cancer
Current Gene Therapy PHB in Cardiovascular and Other Diseases: Present Knowledge and Implications
Current Drug Targets 5-HT5 Receptors
Current Drug Targets - CNS & Neurological Disorders Heparin Affin Regulatory Peptide: A New Target for Tumour Therapy?
Current Cancer Drug Targets