Anti-tumor effect investigation of obtustatin and crude Macrovipera lebetina obtusa venom in S-180 sarcoma bearing mice

Eur J Pharmacol. 2015 Oct 5:764:340-345. doi: 10.1016/j.ejphar.2015.07.011. Epub 2015 Jul 11.

Abstract

Over the last few decades, research on snake venom toxins has provided not only new tools to decipher molecular details of various physiological processes, but also inspiration to design and develop a number of therapeutic agents. Isolated from the venom of Macrovipera lebetina obutusa (MLO), obtustatin represents the shortest known snake venom monomeric disintegrin specific inhibitor of α1β1 integrin. This low molecular weight peptide revealed a potent therapeutic effect on melanoma progression. Its oncostatic effect was related to the inhibition of angiogenesis. The aim of the proposed investigation was to study the influence of obtustatin and crude MLO venom on the S-180 sarcoma growth in vitro and in vivo. A S-180 sarcoma bearing mouse model, histological examination, DNA retardation assay were utilized to investigate the anti-tumor effects of MLO and obtustatin. In addition, some biochemical tests (chemiluminescence-ChL, TBA-test) were applied to elucidate the influence of obtustatin and crude MLO venom on the S-180 sarcoma. The size of tumor was significantly inhibited by MLO venom and obtustatin with the inhibitory rate of 50% and 33% at the doses of 10 µg/mouse and 1mg/kg/day respectively. Both ChL and MDA decrease in the two treated groups. Both obtustatin and MLO venom have an anticancer activity and might be candidates for the treatment of malignant sarcoma. All our results have shown that both obtustatin and MLO venom have an anticancer activity and might be candidates for the treatment of malignant sarcoma.

Keywords: DNA; MLO venom; Obtustatin; S-180 sarcoma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA / metabolism
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Lipid Peroxidation / drug effects
  • Luminescent Measurements
  • Malondialdehyde / metabolism
  • Mice
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Sarcoma, Experimental / drug therapy*
  • Sarcoma, Experimental / genetics
  • Sarcoma, Experimental / pathology
  • Time Factors
  • Tumor Burden / drug effects
  • Viper Venoms / metabolism
  • Viper Venoms / pharmacology*

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Viper Venoms
  • obtustatin, Vipera lebetina obtusa
  • Malondialdehyde
  • DNA