Therapeutic potential of chlorotoxin-like neurotoxin from the Chinese scorpion for human gliomas.
Chlorotoxin, one of the key toxins in scorpion Leiurus 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 IC(50) value of approximately 0.28microM. Under the same conditions, the IC(50) value for normal astrocytes increased to 8microM. 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 0.14microM) 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.
Fu
Yue-Jun
YJ
Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, PR China.
Yin
Li-Tian
LT
Liang
Ai-Hua
AH
Zhang
Chao-Feng
CF
Wang
Wei
W
Chai
Bao-Feng
BF
Yang
Jian-Yi
JY
Fan
Xiao-Jun
XJ
D001253:Astrocytes / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002681:China; D023082:Defensins / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D020128:Inhibitory Concentration 50; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D012604:Scorpion Venoms / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
D023082:Defensins; D012604:Scorpion Venoms; D013778:Tetrazolium Salts; D013844:Thiazoles; C407873:scorpine; C091539:Chlorotoxin; C022616:thiazolyl blue