Recombinantly expressed MeICT, a new toxin from Mesobuthus eupeus scorpion, inhibits glioma cell proliferation and downregulates Annexin A2 and FOXM1 genes

• Published in: Biotechnology letters Vol. 44; no. 5-6; pp. 703 - 712
• Main Authors: Gandomkari, Maryam Shahbazi, Ayat, Hoda, Ahadi, Ali Mohammad
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-06-2022; Springer Nature B.V
• Subjects: Amino Acid Sequence; Amino acids; Animals; Annexin A2 - genetics; Anticancer properties; Applied Microbiology; Bacteria; Binding sites; Biochemistry; Biocompatibility; Biomedical and Life Sciences; Biotechnology; Brain cancer; Brain research; Cell cycle; Cell growth; Cell migration; Cell Proliferation; Chemical bonds; Chemical compounds; Chloride channels; Chloride ions; Cloning; Disulfide bonds; E coli; Gelatinase A; Gene expression; Genes; Glioma; Glioma - drug therapy; Glioma cells; In vivo methods and tests; Invasiveness; Ion channels; Laboratory animals; Life Sciences; Malignancy; Matrix Metalloproteinase 2 - genetics; Mice; Microbiology; Molecular modelling; Original Research Paper; Peptides; Pharmacology; Proteins; RNA, Messenger; Scorpion Venoms - genetics; Scorpions - chemistry; Scorpions - genetics; Toxins; Venom; Recombinant MeICT peptide; Annexin A2; MMP-2; FOXM1; Glioma cells
• ISSN: 0141-5492; 1573-6776
• DOI: 10.1007/s10529-022-03254-x

Gliomas are highly invasive and lethal malignancy that do not respond to current therapeutic approaches. Novel therapeutic agents are required to target molecular mechanisms involved in glioma progression. MeICT is a new short-chain toxin isolated from
Mesobuthus eupeus
scorpion venom. This toxin contained 34 amino acid residues and belongs to chloride channels toxins. In this study, the coding sequence of MeICT was cloned into the pET32Rh vector and a high yield of soluble recombinant MeICT was expressed and purified. Recombinant MeICT-His significantly inhibited the proliferation and migration of glioma cells at low concentration. In vivo studies showed that MeICT was not toxic when administrated to mice at high doses. We also determined the effect of MeICT on the mRNA expression of MMP-2, Annexin A2 and FOXM-2 that are key molecules in the progression and invasion of glioma. Expression of Annexin A2 and FOXM1 mRNA was significantly down-regulated following treatment with MeICT. However, no significant decrease in the expression of MMP-2 gene was identified. In this study a short toxin with four disulfide bonds was successfully produced and its anti-cancer effects was detected. Our findings suggest that recombinant MeICT can be considered as a new potent agent for glioma targeting.