Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications

In the last several decades, there have been significant advances in anticancer therapy. However, the development of resistance to cancer drugs and the lack of specificity related to actively dividing cells leading to toxic side effects have undermined these achievements. As a result, there is considerable interest in alternative drugs with novel antitumor mechanisms. In addition to the recent approach using immunotherapy, an effective but much cheaper therapeutic option of pharmaceutical drugs would still provide the best choice for cancer patients as the first line treatment. Ribosomally synthesized cationic antimicrobial peptides (AMPs) or host defense peptides (HDP) display broad-spectrum activity against bacteria based on electrostatic interactions with negatively charged lipids on the bacterial surface. Because of increased proportions of phosphatidylserine (negatively charged) on the surface of cancer cells compared to normal cells, cationic amphipathic peptides could be an effective source of anticancer agents that are both selective and refractory to current resistance mechanisms. We reviewed herein the prospect for AMP application to cancer treatment, with a focus on modes of action of cationic AMPs.