Chlorotoxin: a helpful natural scorpion peptide to diagnose glioma and fight tumor invasion

Abstract

Chlorotoxin is a small 36 amino-acid peptide identified from the venom of the scorpion Leiurus quinquestriatus. Initially, chlorotoxin was used as a pharmacological tool to characterize chloride channels. While studying glioma-specific chloride currents, it was soon discovered that chlorotoxin possesses targeting properties towards cancer cells including glioma, melanoma, small cell lung carcinoma, neuroblastoma and medulloblastoma. The investigation of the mechanism of action of chlorotoxin has been challenging because its cell surface receptor target remains under questioning since two other receptors have been claimed besides chloride channels. Efforts on chlorotoxin-based applications focused on producing analogues helpful for glioma diagnosis, imaging and treatment. These efforts are welcome since gliomas are very aggressive brain cancers, close to impossible to cure with the current therapeutic arsenal. Among all the chlorotoxin-based strategies, the most promising one to enhance patient mean survival time appears to be the use of chlorotoxin as a targeting agent for the delivery of anti-tumor agents. Finally, the discovery of chlorotoxin has led to the screening of other scorpion venoms to identify chlorotoxin-like peptides. So far several new candidates have been identified. Only detailed research and clinical investigations will tell us if they share the same anti-tumor potential as chlorotoxin.

Figure 1

Amino acid sequence and 3D representation of CTX: (A) Amino acid sequence of CTX with the eight cysteine residues and the four disulfide bridge in orange; (B) 3D structure of CTX, obtain from 1CHL PDB file; α-helix in red, β sheet in blue and disulfide bridge in orange.

Figure 2

3D Representation of CTX and the other chlorotoxin like peptide. 3D structure were obtain from pdb files for Chlorotoxin (1CHL), from model of SWISS-MODEL Repository [65,66,67,68,69] for BmKCta, GaTX1 and GaTx2, and from model build by homology with CTX using @TOME V2 [64] and modeller for AaCtx.