However, the presence of nitro toxins might exasperate the toxicological problems encountered with animals grazing I. lespedezioides. This work was supported by National Institute

for Science and Technology for the Control of Plant Poisonings, CNPq, grant 573534/2008-0. “
“Serine proteases are essential key enzymes in a broad diversity of physiologic and pathologic processes, and their overexpression is tightly blocked by endogenous inhibitors to maintain homeostasis. The disruption of this equilibrium is the basis for disease genesis, and therefore, serine protease inhibitors (SPI) are targets of the synthetic development of drugs (Cuccioloni et al., 2009; Perzborn et al., 2011). The family of Kunitz-type serine

protease inhibitors (Kunitz-type SPI) comprise more than twenty members, which include bovine pancreatic trypsin inhibitor, Alzheimer’s selleck screening library amyloid precursor protein (APP), and tissue factor pathway inhibitors 1 and 2 (TFPI-1 and 2) (Chand et al., 2005). They are competitive protease inhibitors, with one or more Kunitz-type domains, characterized by intrachain disulfide bonds conserved in all family members (Laskowski and Quasim, 2000). The relation of Kunitz-type SPI with cancer development and find more metastases has been shown by reduced levels of endogenous TFPI-2 in some aggressive cancer types (Sierko et al., 2007; Ran et al., 2009) and by reduced tumor cell migration and invasion by TFPI-2 recombinant therapy or TFPI-2 overexpression (Yanamandra et al., 2005; Ran et al., 2009). The proposed mechanisms are related to the inhibition of the expression of matrix metalloproteinase

enzymes and activities (MMPs) Immune system (Rao et al., 1999; Kong et al., 2004; Ran et al., 2009), tumor cell cytotoxicity (Wong et al., 2007; Kemparah and Kisiel, 2008), reduction of tumor cell lymphatic spread (Sierko et al., 2010), and impairment of angiogenesis (Yanamandra et al., 2005; Provençal et al., 2008; Ran et al., 2009). Angiogenesis or neovascularization is a highly complex pathophysiological process, where pre-existing endothelial cells must break through the basement membrane, migrate and proliferate in response to angiogenic factors. The new outgrowths have to reorganize into a patent three-dimensional tubular structure, which will create the new vessel (Risau, 1997). All steps of the process are influenced by a strongly controlled balance of positive or negative modulators, secreted by different cell types, and by the expression of cell membrane adhesion molecules, which allows the perfect cell–cell and cell–extracellular matrix interactions (Ramjaun and Hodivala-Dilke, 2009).