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

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Abstract

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.

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Acknowledgements

We thank Dr. Hossein Asadi for providing U87-MG cell line and Dr. Smayeh Reiisi for technical assistance. This study was supported by Shahrekord University.

Funding

This work was supported by Shahrekord University.

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Authors and Affiliations

  1. Department of Genetics, Shahrekord University, Rahbar Blvd, P O Box 115, 8818634141, Shahrekord, IR, Iran

    Maryam Shahbazi Gandomkari, Hoda Ayat & Ali Mohammad Ahadi

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  1. Maryam Shahbazi Gandomkari
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  2. Hoda Ayat
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  3. Ali Mohammad Ahadi
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Contributions

MSG: investigation, methodology, visualization roles, writing original draft. HA: supervision, conceptualization, project administration, validation, writing, review and editing. AMA: data analysis, writing, review and editing.

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Correspondence to Hoda Ayat.

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All authors declare they have no conflict of interest.

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The permission for experimental animal procedures was obtained from Animal Ethics Committee of Shahrekord University.

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Gandomkari, M.S., Ayat, H. & Ahadi, A.M. Recombinantly expressed MeICT, a new toxin from Mesobuthus eupeus scorpion, inhibits glioma cell proliferation and downregulates Annexin A2 and FOXM1 genes. Biotechnol Lett 44, 703–712 (2022). https://doi.org/10.1007/s10529-022-03254-x

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  • DOI: https://doi.org/10.1007/s10529-022-03254-x

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