, 1997). However, these lectins commonly exhibit distinct affinity for the same ligand (Ramos et al., 2002). As a result, they frequently differ in terms of dose–response activity (Barbosa et al., 2001). Despite the numerous uses of lectins as tools, there are few studies that refer to their antitumor activity or report the underlying mechanisms involved in lectin cytotoxicity. One aspect of this study shows lectins ConA and ConBr to be cytotoxic against both MOLT-4 and HL-60 cells, with IC50 values being approximately 3 μg/ml (ConA) and 20 μg/mL (ConBr) after 72 h of incubation (Table 1). For PBMC, ConA and ConBr

lectins were not cytotoxic at high concentrations (200 μg/ml), demonstrating selectivity for tumor cells (Fig. 2). Several studies have revealed data that corroborates our findings, demonstrating the cytotoxicity of selleck chemical ConA lectin in tumor cells. ConA was shown to be more toxic because it becomes completely tetrameric at physiological pH, exposing its catalytic site better than ConBr. Hence, it is able to exert more pronounced activity than ConBr, which presents as a mixture of dimers and tetramers at physiological pH (Sanz-Aparicio

et al., 1997 and Calvete et al., 1999). In order to identify the mechanism of action Bortezomib chemical structure related to the antiproliferative effect of lectins, genetic toxicity, morphological changes, and experiments of cell death using flow cytometry were conducted.

Comet assay has shown that lectins ConA and ConBr promoted a significant increase in DNA strand breaks in MOLT-4 and HL-60 cells. Since the DNA lesions may disturb the maintenance of genomic integrity, the use of molecules that cause extensive damage to the DNA of these cells can induce programmed cell death and block tumor development (Hanahan and Weinberg, 2000, Hoang et al., 2007 and Leonetti and Zupi, 2007). The morphological analysis by differential staining with EB/AO demonstrated that cells treated with the lectins (ConA and ConBr) predominantly showed specific apoptosis features, as opposed to necrosis. Once again, our findings (Fig. 3) are supported by previous studies on the apoptotic effects of lectins (Barbosa et 17-DMAG (Alvespimycin) HCl al., 2001, Gastman et al., 2004, Kulkarni et al., 1998, Liu et al., 2009a, Liu et al., 2009b and Liu et al., 2009c). An important marker of cell death by apoptosis is the internucleosomal cleavage of chromatin and the fragmentation of DNA by DNases, such as the Apoptosis Induction Factor (AIF), endonuclease G, and caspase-activated DNase (CAD). These DNases are released from the mitochondria during apoptosis and are then translocated to the nucleus to promote DNA fragmentation (Elmore, 2007). The apoptotic nuclei can be distinguished by their hypodiploid DNA content, compared with the diploid DNA content of normal cells (Cury-Boaventura et al., 2003).