F۲ peptide fraction of Androctonus crassicauda scorpion venom: Inducing M۲ to M۱ 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-۲۶ 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 M۲ phenotype and characterized by flow cytometry. Real-time PCR and ELISA quantified M۱ and M۲ macrophage-associated gene and cytokine expression. The impact of venom fractions on CT-۲۶ cell proliferation and migration was assessed via MTT and wound-healing assays. Phagocytic activity was evaluated using a yeast phagocytosis assay.Results: The F۲ venom fraction significantly upregulated pro-inflammatory gene and cytokine expression, and downregulated anti-inflammatory gene and cytokine expression in M۲ macrophages. Furthermore, the F۲ fraction significantly inhibited CT-۲۶ cell proliferation and migration. Critically, it also enhanced the phagocytic capacity of M۲ macrophages.Conclusion: Our results suggest that the F۲ fraction of A. crassicauda scorpion venom reprograms tumor-associated M۲ macrophages towards an anti-tumor M۱ phenotype. These findings suggest the potential of the F۲ 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.

کلیدواژه ها:

Colorectal cancer ، Scorpion venom ، Androctonus crassicauda Cancer therapy ، Macrophage polarization