It is water-soluble and its aggregation of monomeric selleck products melittin to a tetramer is promoted by high salt, high melittin concentration, and high pH ( Raghuraman and Chattopadhyay, 2007). There is substantial evidence that melittin can permeabilize cell membranes by inducing pore formation and lyse prokaryotic and eukaryotic cells in a non-selective manner ( Raghuraman and

Chattopadhyay, 2007; Papo and Shai, 2003). This mechanism of action is responsible for the hemolytic, anti-microbial ( Bechinger, 1997; Blondelle and Houghten, 1991; Chicharro et al., 2001; Díaz-Achirica et al., 1998; Lazarev et al., 2002; Luque-Ortega et al., 2003; Pérez-Cordero et al., 2011; Tosteson et al., 1985) and anti-tumor ( Holle et al., 2009; Li et al., 2006; Winder et al., 1998) activities of melittin. The melittin peptide has been shown to exhibit strong inhibitory activity against the protozoan parasite Leishmania ( Akuffo et al., 1998; Pérez-Cordero et al., 2011). Interestingly, it has selleckchem been shown that cecropin A–melittin hybrid peptides present remarkable leishmanicidal activity with minimal cytotoxic activity against host cells ( Chicharro et al., 2001; Díaz-Achirica

et al., 1998; Luque-Ortega et al., 2003) even in vivo ( Alberola et al., 2004; Luque-Ortega et al., 2001). Thus far, only three studies have shown the lytic effects of melittin on T. cruzi epimastigotes and trypomastigotes ( Azambuja et al., 1989; Jacobs et al., 2003; MG-132 molecular weight Fieck et al., 2010). However, none of these studies investigated the effects of mellitin on parasite morphology, including the

cell death phenotype. Furthermore, only the study by Jacobs et al. (2003) considered the effects of melittin on host cells, where it was shown to be non-toxic to glioblastoma cells. Recently, our group showed that A. mellifera crude venom could affect the viability and ultrastructure of all T. cruzi developmental forms, including the intracellular amastigotes, at concentrations that were approximately 100-fold lower than those required to cause toxicity in mammalian cells ( Adade et al., 2012). Interestingly, the venom-treated parasites exhibited different programmed cell death pathways; autophagic cell death appeared to be the predominant death mechanism in epimastigotes, whereas venom-treated trypomastigotes appeared to undergo apoptotic cell death. In the present work, we (i) investigated our hypothesis that the melittin component of A. mellifera venom was responsible for parasite damage and for the different cell death profiles observed in epimastigotes and trypomastigotes and (ii) more carefully examined the effects of melittin on the growth of all T. cruzi developmental forms, including the intracellular amastigotes.