The search for new drugs and treatment approaches is of particular importance for glioblastomas (GBMs), as with other types of malignant gliomas, as they are lethal without the available medical care. Current anticancer cocktails have failed to prolong survival beyond 1 year, in part owing to the natural resistance of GBM cells and to the toxic side effects of the available drugs. In many organisms, cell death can be induced by cytolysins, which are proteins that can form pores in biological membranes. Perhaps by facilitating drugs to enter into the cytosol, cytolysins might be used to increase the efficacy of conventional anticancer agents. Here, the cytotoxicity of two sea anemone pore-forming cytolysins, toxin Bc2, and equinatoxin (EqTx-II) were investigated. Toxin Bc2 and EqTx-II were cytotoxic against human U87 and A172 GBM cell lines either wild type or p53 mutant, a tumor suppressor frequently mutated in malignant gliomas. Moreover, noncytotoxic concentrations of Bc2 or EqTx-II potentiated the cytotoxicity induced by low dose concentrations of all classical chemotherapeutics agents tested: cytosine arabinoside, doxorubicin, and vincristine. In comparison with the cytotoxicity induced by each of these classical anticancer drugs alone, 10–300-fold less of the therapeutic drug was needed when combined with the cytolysins. These results are promising, since lower concentrations of chemotherapeutic drugs could reduce the adverse effects of chemotherapy.
aDepartamento de Anatomia, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro
bDepartamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
cBiotechnical Faculty, Department of Biology, University of Ljubljana, Ljubljana, Slovenia
Correspondence to Nelson H. Gabilan, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, 88040-9000, Santa Catarina, Brazil
Tel: +55 48 3721 9589; fax: +55 48 3721 9672;
*Vivaldo Moura Neto and Nelson H. Gabilan contributed equally to this work.
Vivaldo Moura Neto: Tel: +55 21 2562 6465; fax: +55 21 2290 0587; e-mail: firstname.lastname@example.org
Received 20 April 2007 Revised form accepted 29 January 2008