During the last two decades cationic amphiphilic
peptides and
peptide sequences (CAPs) with
cancer-selective toxicity have appeared. Based on their spectrum of anticancer activity CAPs can be divided into two major classes. The first class includes
peptides that are highly potent against both bacteria and
cancer cells, but not against mammalian cells. The second class includes
peptides that are toxic to bacteria, and both mammalian
cancer and non-
cancer cells. Most antimicrobial and anticancer CAPs share a common membranolytic mode of action that results either in the selective disruption of the
cancer cell membrane or permeation and swelling of mitochondria. The electrostatic attraction between the negatively charged membrane components of bacterial and
cancer cells and CAPs is believed to play a crucial role in the disruption of bacterial and
cancer cell membranes. This mode of action appears to bypass established resistance mechanisms. However, it is currently unclear as to why some CAPs kill
cancer cells when others do not. In addition, non-membranolytic mode of actions of CAPs is increasingly recognized to contribute significantly to the anticancer activity of certain CAPs. The development of CAP-based chemotherapeutics is complicated due to the traditionally poor pharmacokinetic properties and high manufacturing costs of
peptides and the low intrinsic selectivity for
cancer cells.
Peptidomimetic approaches combined with novel selective delivery devices show promise in overcoming some of these obstacles. Furthermore, the ability of CAPs to bypass established resistance mechanisms provides an attractive strategy to develop novel lead structures for
cancer treatment.