Prostate and colon cancer represent a major health problem worldwide. In the present study, we evaluated the anticancer\nproperties and cytotoxicity of Cerastes-cerastes (CC) snake venom on colon (Caco-2) and prostate (PC-3) cancer cells\nafter their pretreatment with variable concentrations of Bacillus Calmette-Gu�©rin (BCG) derived purified protein derivative\n(PPD). We monitoned the cell cycle arrest profile and specific cellular apoptosis markers (i.e. pro- and anti-apoptotic genes P53,\nBax and Bcl-2 in CC- and BCG/PPD-pretreated cells using real time PCR. The cytotoxicity was determined by using MTT assay.\nOur data show that 24 h-treatment of cancer cells with CC venom induced a concentration-dependent cytotoxicity with IC50\nvalues of 60 (Caco-2 cells) and 81 (PC-3 cells) �¼g/ml. Interestingly, addition of BCG/PPD at 25 and 50 �¼g/ml markedly increased\nthe CC venom-induced toxicity on cancer cells, with IC50 values of 1.04 and 0.59 �¼g/ml for Caco-2 (up to 102-fold increase) or\n2.78 and 0.70 �¼g/ml for PC-3 cells (up to 116-fold increase). By analyzing the cell cycle arrest and related gene expression\npattern, the main phase of cell cycle arrest was found to be G2/M in both cell lines. An S-phase arrest was also observed in PPD\npretreated colon Caco-2 cell line to a greater extent than that observed in cells only treated with CC venom. Up regulation of proapoptotic\nand down regulation of anti-apoptotic genes in PPD pretreated cells were significantly enhanced as compared to cells\ntreated with CC venom alone. In this study, we suggest that PPD -via its synergistic action with the CC venom-might be used as\nan enhancer of the anti-cancer properties of CC venom.
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