Synthetic Peptides Induce Human Colorectal Cancer Cell Death via Proapoptotic Pathways

Cancer resistance to drugs and chemotherapy is a problem faced by public health systems worldwide. Repositioning antimicrobial peptides could be an efficient strategy to overcome that problem. This study aimed at repurposing antimicrobial peptides PepGAT and PepKAA for cancer treatment. After screening against several cancers, PepGAT and PepKAA presented IC50 values of 125.42 and 40.51 μM at 72 h toward colorectal cancer (CRC) cells. The mechanisms of action revealed that both peptides induced cell cycle arrest in G2/M and drove HCT-116 cells to death by triggering apoptosis. qPCR analysis revealed that peptides modulated gene expression in apoptosis, corroborating the data from caspase 3/7 and flow cytometry experiments. Yet, peptides induced ROS overaccumulation and increased membrane permeabilization, pore formation, and loss of internal content, leading to death. Additionally, peptides were able to inhibit cell invasion. Previous studies from the same group attested to no toxicity to normal human cells. Thus, PepGAT and PepKAA have great potential as anticancer molecules.