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.

Scorpion toxin peptide action at the ion channel subunit level

“…Such development has obvious implications towards the treatment of a range of chronic medical conditions including neurodegenerative and cardiovascular disease (Fuller et al, 2007). Cancer therapy also benefits from SCTX research, where Chlorotoxin (Leiurus quinquestriatus), a small conductance chloride ion channel inhibitor, has been modified for use as a targeted radiotherapy agent and imaging peptide, and is currently under clinical trial for use against a range of cancers (Dardevet et al, 2015;Stroud et al, 2011). Similarly discovery and modification of SCTX peptides and componds similar to Kurtoxin, that selectively target voltagegated calcium channels, protend significant advances in chronic pain management (Swayne and Bourinet, 2008).…”

“…Previous reviews have focused on the structural, computational, and molecular analysis of scorpion venom components and ion channel interactions (Smith et al, 2014;Gurevitz et al, 2014), as well as functional comparison of their actions on ion channels. Although some reviews have outlined a broad overview of SCTX peptide action Quintero-Hernandez et al, 2013;du Plessis et al, 2008), the majority have provided relatively detailed information of SCTX action within particular ion channel subfamilies, such as sodium channels Gordon et al, 2007;Pedraza Escalona and Possani, 2013;Pucca et al, 2015a;Gilchrist and Bosmans, 2012;Gordon and Gurevitz, 2003), potassium channels MartinEauclaire and Bougis, 2012;Jimenez-Vargas et al, 2012a;Bartok et al, 2015;Yu et al, 2016;Bougis and Martin-Eauclaire, 2015;Yang et al, 2015;Wang et al, 2014;Wanke and Restano-Cassulini, 2007), and to a lesser extent, calcium Norton and McDonough, 2008;Ramos-Franco and Fill, 2016), and chloride channels Dardevet et al, 2015). This review establishes a comprehensive comparison of the broad range of functionally-validated SCTX peptide actions across the breadth of ion channel families.…”

Tailored nanocarriers and bioconjugates for combating glioblastoma and other brain tumors

“…[109] Toxins: targeting agents and a potential treatment Disintegrins, a group of snake venom toxins, have the potential to block cancer cell migration and invasion by interaction with integrins. [110] Contortrostatin, a snake venom disintegrin, was proven to inhibit tumor growth and angiogenesis and to prolong survival in a rodent glioma model by Pyrko et al [111] Similarly, scorpion venoms has been used in targeting brain tumors, in tumor painting, and in cell sensitization to chemotherapy. [112][113][114] Chlorotoxin (CTX) is a promising tool for glioma management.…”

“…[119] CTX is a highly diffusible peptide that can cross the BBB or the BBTB with, to date, no evident signs of toxicity for normal human cells. [110] Coated iron superoxide particles conjugated to CTX may be used as a MRI contrast agent as well as for delivering therapeutic agents (e.g. O6-benzylguanine and siRNA) to glioma cells.…”

Efficacy in Treating Lung Metastasis of Invasive Breast Cancer with Functional Vincristine Plus Dasatinib Liposomes

“…The process of metastasis includes several steps, involving cell adhesion, invasion, proliferation, and vessel formation [9,10]. Invasion is the ability of cancer cells to infiltrate and/or spread to the surrounding normal tissues, and consists of cell migration and degradation of extracellular matrix [11]. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, play a major role in remodeling of extracellular matrix structures [12].…”