Synergistic Inhibition of Colorectal Cancer Cells by Autocrine Motility Factor Peptide and Glycyrrhetinic Acid

Abstract

Background: Anti-cancer peptides are a powerful drug concept that induces cancer cell death through growth inhibition and membrane disruption, providing broad efficacy. The autocrine motility factor (AMF) interacts with the AMF receptor, regulating cancer cell motility, proliferation, metastasis, and angiogenesis through autocrine and paracrine pathways. However, studies verifying the synergistic effect of the combined use of anti-cancer drugs extracted from plants and AMF treatment are insufficient. Methods: The effects of AMF-derived peptide sequences were evaluated in HT29 and SW620 colorectal cancer (CRC) cell lines. The study assessed the impact of AMF peptides on cell proliferation, colony formation, the Nicotinamide Adenine Dinucleotide Phosphate/Reduced Nicotinamide Adenine Dinucleotide Phosphate (NADP+/NADPH) ratio, and reactive oxygen species (ROS) generation in these CRC cells. Additionally, the combined effect of AMF peptides and glycyrrhetinic acid (GA), a compound derived from licorice plants, was investigated by analyzing cell proliferation, colony formation, ROS production, and cell cycle progression in CRC cells. Results: AMF peptides significantly inhibited CRC cell growth (p <0.05), decreased colony formation (p < 0.05), and increased the NADP+/NADPH ratio (p < 0.05) and ROS production (p < 0.001). When combined with GA, AMF peptides enhanced GA's effects on CRC cells, further suppressing cell growth (p < 0.05) and colony formation (p < 0.05) while increasing ROS generation (p < 0.05). Conclusion: The synergy between AMF peptides and GA, derived from licorice plants, suggests the potential for combined peptide-phytochemical therapy for treating CRC.