Inhibition of breast cancer cell metastasis by low molecular weight fractions of Hottentotta zagrosensis scorpion venom through targeting the epithelial-mesenchymal transition

Document Type : Original Article

Authors

1 PhD Candidate, Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

3 Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Jundishapur University of Medical Sciences, Ahvaz, Iran

4 Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Ahvaz, Iran

Abstract
The epithelial-mesenchymal transition is a key molecular process in the development of metastasis in breast cancer. The aim of this study was to purify low molecular weight peptides derived from scorpion venom (PESV) from the venom of Hottentotta zagrosensis and to evaluate their anti metastatic potential in the human breast cancer cell line Michigan Cancer Foundation. Scorpion venom was fractionated using Fast Performance Liquid Chromatography and ultrafiltration. The separated fractions were loaded onto Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis and stained with silver nitrate. This process identified protein bands with molecular weights below 10.00 kDa, which were subsequently analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Western blotting. Michigan Cancer Foundation cells were exposed to 10.00 and 20.00 µg mL-1 of PESV, and their effects on the expression of E cadherin, N cadherin, Vimentin, Snail and Twist proteins were evaluated by Western blotting. The treatment significantly increased the epithelial marker E cadherin, while simultaneously reduced the mesenchymal markers N cadherin and Vimentin as well as the transcription factors Snail and Twist. These changes in PESV treated groups were dose dependent, and at 20.00 µg mL-1 the effect was comparable to that of cisplatin. In conclusion, these findings suggested that PESV, extracted from the venom of H. zagrosensis, effectively suppressed the aggressive phenotype of cancer cells while promoting their reversion to an epithelial state. The preclinical evidence demonstrated that this peptide markedly inhibited metastasis, underscoring its potential as a promising therapeutic candidate for breast cancer.

Keywords

Subjects

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Volume 17, Issue 10
October 2026
Pages 739-746

  • Receive Date 29 December 2025
  • Accept Date 11 July 2026