Fractionation and characterization of Cerastes cerastes cerastes snake venom and the antitumor action of its lethal and non-lethal fractions

In the present study fractionation of the Cerastes cerastes cerastes snake venom by gel filtration on Sephadex G-75 gave 14 protein fractions. Phospholipase PLA(2) activity is not uniformly correlated with the lethality to mice in regard to all venom fractions. F11 which is the richest in PLA(2) activity is less toxic than F3, which contains a small amount of PLA(2), and F12 is the lowest in lethality and PLA(2) activity. Treatment of Ehrlich ascites-bearing mice with two i.p. injections of the most lethal fraction (173) or a non-lethal fraction (174) resulted in a significant antitumor activity demonstrated by an increase in the mean survival time of the animals (22.5 and 27.9 days) and in the tumor inhibition ratio of tumor growth (T/C\% 139 and 172, respectively), compared to tumor-bearing controls. The cytotoxic activity of F3 and F4 against Ehrlich ascites carcinoma cells might be due to the presence of a cytotoxin rather than to the direct cytolytic effect of the PLA(2) because the non-lethal F4 is free from PLA(2). Treatment of Swiss albino mice with two i.p. injections of F3 or F4 at the adopted dose levels produced no detrimental side effects demonstrated by the insignificant changes in the tested serum and liver parameters. Treatment of the tumor-bearing mice with the same venom fractions significantly modulated all of the studied biochemical parameters in the serum and liver tissues, compared to normal controls. (C) 2003 Elsevier Ltd. All rights reserved.