In Vitro Cytotoxic and Proapoptotic Activities of Anatolian Macrovipera Lebetina Obtusa (Dwigubski, 1832) Crude Venom on Cultured K562 Human Chronic Myelogenous Leukemia Cells

Abstract

In the context of searching for anticancer compounds in natural products, snake venom is one of the important sources for peptide/protein based bioactive molecules. Proteins and peptides with anticancer activity were purified and identified from snake venoms. The aim of the present study was to determine the in vitro cytotoxicity of Macrovipera lebetina obtusa (Blunt-Nosed Viper) crude venom from southeastern Anatolia against K562 human chronic myelogenous leukemia (CML) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Adenosine tripohsphate (ATP) assays. Additionally, the apoptosis induction was assessed by morphological evaluation and immunohistochemical analysis for activated caspase-3. For histopahtological evaluation, haematoxylineosin, giemsa and papanicolau stains were used in combination. M. L obtusa venom showed dose-dependent toxicity against K562 cells after 72 h treatment with different concentrations of crude venom. 1050 values were 0.45 and 0.37 mu g/mL for MTT and ATP assays, respectively. Nuclear fragmentation and condensation, apoptotic bodies and activation of caspase-3, as an induction of apoptosis were also observed in K562 cells. Since apoptosis-inducing compounds are important for the treatment of cancer, further studies on Anatolian M. I. obtusa venom could result in the purification and identification of new proteins and peptides, which might have therapeutic value for the treatment of CML.