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Crude preparations as well as purified components of venoms isolated from American, Asian and European snakes have been shown to inhibit the growth of some mouse and human cancer cell lines. However, it is not known if Cerastes cerastes venom (CCV) obtained from the Egyptian desert possesses any anti-tumor activity. In the present study we examined in vitro the effect of CCV on the growth rate and morphology of a mouse mammary tumor virus-induced mammary tumor cell line (RIII/Sa-MT). In addition, the effect of the venom on the growth of RIII/Sa-MT cells transplanted into syngeneic mice was investigated. Our results show that CCV at a concentration of 7 mu g/ml kills in vitro a significant number of cells (approximate to 55%) within a period of 48 h. CCV (1 mu g/mouse), administered once per week directly into growing tumors for a period of 4 weeks, was found to reduce tumor load by 54%, and as a consequence the CCV-treated mice lived for more than 35 days longer than untreated mice. Histological and ultrastructural examination of the cells and tumors, as well as nuclear staining of the cells and DNA fragmentation studies, led us to conclude that necrosis is most likely the underlying mechanism by which CCV inhibited the growth of mouse mammary tumor cells both in vitro and in vivo. (C) 2009 Elsevier Ltd. All rights reserved.