Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential

Scientific Reports
Tengfei XuNicolai E Savaskan

Abstract

Brain tumors are fast proliferating and destructive within the brain microenvironment. Effective chemotherapeutic strategies are currently lacking which combat this deadly disease curatively. The glioma-specific chloride ion channel represents a specific target for therapy. Chlorotoxin (CTX), a peptide derived from scorpion venom, has been shown to be specific and efficacious in blocking glioma Cl(-) channel activity. Here, we report on two new derivatives (termed CA4 and CTX-23) designed and generated on the basis of the peptide sequence alignments of CTX and BmKCT. The novel peptides CA4 and CTX-23 are both effective in reducing glioma cell proliferation. In addition, CTX, CA4 and CTX-23 impact on cell migration and spheroid migration. These effects are accompanied by diminished cell extensions and increased nuclear sizes. Furthermore, we found that CA4 and CTX-23 are selective with low toxicity against primary neurons and astrocytes. In the ex vivo VOGiM, which maintain the entire brain tumor microenvironment, both CTX and CA4 display anti-tumor activity and reduce tumor volume. Hence, CTX and CA4 reveal anti-angiogenic properties with endothelial and angiogenic hotspots disrupting activities. These data report on the identi...Continue Reading

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Citations

Apr 9, 2016·Oncotarget·Zheng FanNicolai E Savaskan
Oct 8, 2016·Journal of Translational Medicine·Antonella BiasiottaAntonio Facchiano
Feb 8, 2018·Physiological Reviews·Natalia PrevarskayaYaroslav Shuba
Apr 7, 2020·Journal of Applied Toxicology : JAT·Erasto Desales-SalazarRaymundo Rene Rivas-Caceres

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Methods Mentioned

BETA
PCR
dissection
surgical resections

Software Mentioned

MS Excel
Image J
× Fluor4
Tecan
cell

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