F2 peptide fraction of Androctonus crassicauda scorpion venom: Inducing M2 to M1 macrophage polarization and inhibiting colon carcinoma cell proliferation and migration

Ghadiri, Noushin; Rashno, Mohammad; Khodadadi, Ali; Asadirad, Ali; Nemati, Mohammad; Ghadiria, Ata A.

doi:10.22038/ajp.2025.25721

F2 peptide fraction of Androctonus crassicauda scorpion venom: Inducing M2 to M1 macrophage polarization and inhibiting colon carcinoma cell proliferation and migration

Document Type : Original Research Article

Authors

Noushin Ghadiri ¹

Mohammad Rashno ¹

Ali Khodadadi ¹

Ali Asadirad ¹

Mohammad Nemati ²

Ata A. Ghadiria ¹

¹ Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

² Department of Venomous Animals and Anti-venom Production, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Ahvaz, Iran

10.22038/ajp.2025.25721

Abstract

Objective: Colorectal cancer (CRC) is among the deadliest malignancies, often diagnosed at advanced stages, limiting treatment efficacy and necessitating alternative therapeutic approaches. Scorpion venom has emerged as a promising source of bioactive compounds for cancer therapy. This study investigated the anti-cancer potential of Androctonus crassicauda scorpion venom fractions against CT-26 colon cancer cells.
Materials and Methods: A. crassicauda venom fractions were isolated using gel filtration chromatography. Murine peritoneal macrophages, harvested from BALB/c mice, were polarized towards the M2 phenotype and characterized by flow cytometry. Real-time PCR and ELISA quantified M1 and M2 macrophage-associated gene and cytokine expression. The impact of venom fractions on CT-26 cell proliferation and migration was assessed via MTT and wound-healing assays. Phagocytic activity was evaluated using a yeast phagocytosis assay.
Results: The F2 venom fraction significantly upregulated pro-inflammatory gene and cytokine expression, and downregulated anti-inflammatory gene and cytokine expression in M2 macrophages. Furthermore, the F2 fraction significantly inhibited CT-26 cell proliferation and migration. Critically, it also enhanced the phagocytic capacity of M2 macrophages.
Conclusion: Our results suggest that the F2 fraction of A. crassicauda scorpion venom reprograms tumor-associated M2 macrophages towards an anti-tumor M1 phenotype. These findings suggest the potential of the F2 fraction of A. crassicauda scorpion venom as a novel therapeutic strategy for the treatment of colon cancer. However, to confirm this potential, further in vivo studies need to be carried out.

Keywords

Colorectal cancer

Scorpion venom

Androctonus crassicauda Cancer therapy

Macrophage polarization

Subjects