Therapeutic potential of chlorotoxin-like neurotoxin from the Chinese scorpion for human gliomas

Chlorotoxin. one of the key toxins in scorpion Lehirus quinquestriatus venom, has been shown to bind specifically to glioma cell surface as a specific chloride channel blocker. In this study, a purified, recombinant chlorotoxin-like peptide from the scorpion Buthus martensii Karsch (named rBmK CTa) was characterized by in vivo and in vitro studies. The results from cell proliferation assay with human glioma (SHG-44) cells showed that rBmK CTa inhibits the growth of glioma cells in a dose-dependent manner, with an IC50 value of approximately 0.28 mu M. Under the same conditions, the IC50 value for normal astrocytes increased to 8 mu M. This clearly indicated that rBmK CTa had specific toxicity against glioma cells but not astrocytes. Results from whole-cell patch-clamp recording showed that chloride current in SHG-44 was inhibited by rBmK CTa in a voltage-dependent manner and percent inhibitions for the blocking action of rBmK CTa (0.07 and 0.14 mu M) on I-Cl was 17.64 +/- 3.06% and 55.86 +/- 2.83%, respectively. Histological analysis of rBmK CTa treated mice showed that brain, leg muscle and cardiac muscle were the target organs of this toxin. These results suggest that rBmK CTa may have potential therapeutic application in clinical treatment of human glioma. It represents an approach for developing a novel therapeutic agent. (c) 2006 Elsevier Ireland Ltd. All rights reserved.