title: Equinatoxin II potentiates temozolomide- and etoposide-induced glioblastoma cell death.
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.
authors.affiliation: Instituto de Ciências Biomédicas, CCS - Bloco F, Universidade Federal do Rio de Janeiro, 21949-590, Rio de Janeiro, Brazil.
authors.forename: Suzana Assad
authors.initials: SA
authors.lastname: Kahn
authors.forename: Deborah
authors.initials: D
authors.lastname: Biasoli
authors.forename: Celina
authors.initials: C
authors.lastname: Garcia
authors.forename: Luiz Henrique M
authors.initials: LH
authors.lastname: Geraldo
authors.forename: Bruno
authors.initials: B
authors.lastname: Pontes
authors.forename: Morgana
authors.initials: M
authors.lastname: Sobrinho
authors.forename: Ana Carina Bon
authors.initials: AC
authors.lastname: Frauches
authors.forename: Luciana
authors.initials: L
authors.lastname: Romão
authors.forename: Rossana C
authors.initials: RC
authors.lastname: Soletti
authors.forename: Fernando dos Santos
authors.initials: Fdos S
authors.lastname: Assunção
authors.forename: Fernanda
authors.initials: F
authors.lastname: Tovar-Moll
authors.forename: Jorge Marcondes
authors.initials: JM
authors.lastname: de Souza
authors.forename: Flavia R S
authors.initials: FR
authors.lastname: Lima
authors.forename: Gregor
authors.initials: G
authors.lastname: Anderluh
authors.forename: Vivaldo
authors.initials: V
authors.lastname: Moura-Neto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D003064:Cnidarian Venoms / Q000494:pharmacology*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D003064:Cnidarian Venoms; C012307:equinatoxin; D005047:Etoposide; D003606:Dacarbazine; D000077204:Temozolomide