Cancer causes over seven million deaths annually and presents significant treatment challenges, particularly in advanced stages where it is often incurable. Current therapies can lead to severe side effects and drug resistance. Antimicrobial peptides (AMPs) have emerged as a promising area of research for new anti-cancer agents, as they are part of the innate immune system and exhibit anti-cancer properties alongside their pathogen-targeting abilities. This study explored the efficacy of various natural AMPs against equine sarcoid and human prostate cancer cell lines, aiming to understand their mechanisms of action. Cytotoxicity assays and real-time measurements revealed strong activity of the AMPs against both cancer types. Notably, derivatives of peptide NK-2 showed enhanced anti-cancer effects, indicating their potential for drug development. The investigation into the peptides' mechanisms revealed that they primarily induce cell death through direct membrane destruction, targeting the anionic surfaces common in many cancer cells. The study also found that AMPs can differentiate between various anionic cell surface structures, binding more effectively to sulfated carbohydrates. While the peptides demonstrated selectivity for prostate cancer cells over healthy cells, they did not show the same selectivity for equine sarcoid cells, likely due to the absence of anionic surfaces in those cancer cells.
