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

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.