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Updated: May 16, 2026

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
Equinatoxin II potentiates temozolomide- and etoposide-induced glioblastoma cell death
Suzana Assad Kahn1, Deborah Biasoli, Celina Garcia
1Instituto de Ciências Biomédicas, CCS - Bloco F, Universidade Federal do Rio de Janeiro, 21949-590, Rio de Janeiro, Brazil.
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.
Insights
Equinatoxin II (EqTx-II), a sea anemone toxin, enhances chemotherapy for glioblastoma (GBM). This novel approach potentiates temozolomide and etoposide effectiveness, showing promise for improved GBM treatment with reduced side effects.
Area of Science:
- Neuro-oncology
- Pharmacology
- Toxicology
Background:
- Glioblastoma (GBM) presents significant treatment challenges due to inherent chemoresistance.
- Current GBM therapies offer limited efficacy, necessitating innovative treatment strategies.
- Understanding GBM resistance mechanisms is crucial for developing improved therapeutic approaches.
Purpose of the Study:
- To investigate the potential of equinatoxin II (EqTx-II) in enhancing the efficacy of standard GBM chemotherapies.
- To explore the underlying molecular mechanisms of EqTx-II's potentiating effect on GBM cells.
- To evaluate the in vivo efficacy of combined EqTx-II and chemotherapy in a GBM model.
Main Methods:
- Treatment of GBM cells with non-cytotoxic concentrations of EqTx-II in combination with temozolomide (TMZ) and etoposide (VP-16).
- Assessment of cellular cytotoxicity and investigation of the PI3K/Akt signaling pathway.
- In vivo studies using Magnetic Resonance Imaging (MRI) to monitor GBM tumor growth inhibition.
Main Results:
- Non-cytotoxic EqTx-II significantly potentiated the cytotoxic effects of both TMZ and VP-16 on GBM cells.
- The observed potentiation was selective to GBM cells and linked to PI3K/Akt pathway inhibition.
- In vivo MRI demonstrated that EqTx-II enhanced VP-16's ability to inhibit GBM tumor growth.
Conclusions:
- Combined therapy with EqTx-II and chemotherapy offers a promising new strategy for GBM treatment.
- This approach may allow for lower doses of chemotherapeutic agents, potentially reducing adverse effects.
- EqTx-II represents a valuable tool for enhancing the effectiveness of current GBM treatments.
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