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Current Topics in Medicinal Chemistry
ISSN (Print): 1568-0266
ISSN (Online): 1873-5294
VOLUME: 12
ISSUE: 19
DOI: 10.2174/1568026611212190006      Price:  $58









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

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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
Pages 2082-2093 (12)
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.
Affiliation:
Instituto de Ciencias Biomedicas, CCS - Bloco F, Universidade Federal do Rio de Janeiro, 21949-590, Rio de Janeiro, Brazil.