, 2001, Girisk and Kemparaju, 2007 and Matsushita and Okabi, 2001). Other peptides that have been isolated are the oxyopinins from the wolf spider Oxyopes kitabensis, which form pores in lipid membranes ( Belokoneva et al., 2003 and Corzo et al., 2002) and, considering the anti-tumor action of other pore-forming peptides,

oxyopinins could also be considered as good candidates for anti-cancer therapy ( Duke et al., 1994 and Shaposhnikova et al., 1997). It is known that many toxins rely on the influx of ions through the plasma membrane in order to act as anti-cancer agents ( Tu et al., 2008), and many peptides isolated from spider venoms act MAPK inhibitor blocking ion channels, such as ω-ACTX-1- and ω-ACTX-2-type toxins from funnel-web spiders, which selectively block insect calcium channels ( Tedford et al., 2004), and Protoxins

I and II from Thrixopelma pruriens, that act on Na+ channels. These are just a few examples of the great number of toxins found in spider venoms that KU-60019 supplier have not yet been the subject of anti-cancer research and that could represent an advance in this science field. Among the studies that report the effects of spider venom using in vivo and in vitro tumor models, a paper published by Gao et al. (2005b) is notable, in which the authors verified the effects of the venom of Macrothele raven (Araneae, Hexathelidae) upon the proliferation and cytotoxicity of human cervical carcinoma cells (HeLa). Spider venom at doses of 40, 20, and 10 mg/l significantly decreased cell proliferation in HeLa cells, in a dose- and time-dependent manner; furthermore, these same Isoconazole doses significantly increased cytotoxicity as determined by LDH release from the cells. There was an arrest in cell cycle and activation

of caspase-3 in treated cells, leading to apoptosis. The authors also investigated the in vivo effect of the venom, using nude mice subcutaneously injected with HeLa cells. In the groups injected with various concentrations of spider venom by the tail vein, the size of the tumor inside the skin was significantly smaller than in untreated mice. A similar study was performed using the same venom on the human breast carcinoma cell line MCF-7 (Gao et al., 2007). Through the [3H]-methyl thymidine incorporation assay it was shown that the venom affected cell viability in a dose- and time-dependent manner. The venom, at doses of 10, 20, and 40 μg/ml, lead these cells to death both by necrosis and apoptosis, which could be verified by flow cytometry that also showed cell cycle arrest in the G2/M and G0/G1 phases. In vivo, the venom, at doses of 1.6, 1.8, and 2.0 μg/g, reduced tumor size compared to control in mice after 21 days of treatment.