In a cystic fibrosis xenograft model, gene transfer of hCAP18/LL-37 restored bacterial killing to normal levels [68]. This report suggests that hCAP18/LL-37 may confer protection against bacterial infections in vivo. In Candida Raf inhibition albicans, LL-37 can disrupt the cell wall and the cell membrane. Thus, peptide-induced membrane permeabilization increases the inhibition of C. albicans growth [69], [70] and [71]. HDPs are known to contain some antiviral activity. For example, β-sheet peptides such as defensins, tachyplesin, and protegrins provoked remarkable inactivation of HSV [72]. Furthermore, α-helical

peptide as LL-37 inhibits virus replication against vaccinia (smallpox) virus [73]. In addition, LL-37 exhibits antiviral activity against HSV-1 in corneal and conjunctival epithelia [74]. Existing chemotherapeutic drugs that are widely used in cancer treatment have the severe side effect of nonspecific cytotoxicity. These agents target any rapidly dividing cells, without discriminating between healthy and

cancerous cells. Furthermore, many cancers eventually become resistant to conventional chemotherapy through selection for multidrug-resistant variants [75]. Thus, there is an urgent need to develop new antitumor drugs with new modes of action that selectively target the cancerous cells. Most HDPs have a cationic amphipathic structure, and they preferentially bind and insert into the negatively charged surfaces of bacterial cell membranes. The consequent destabilization click here of the membranes disturbs electrolyte balance and causes leakage of the intercellular contents, leading to cell death. Normal mammalian cell membranes generally have a neutral net charge, and their

membranes are enriched in phosphatidylethanolamine (PE), phosphatidylcholine (PC), sphingomyelin (SM), and cholesterol. Parvulin In contrast, bacterial cell membranes are negatively charged with higher proportions of phosphatidylglycerol (PG), cardiolipin (CL), and phosphatidylserine (PS), and have lower cholesterol content [76]. Thus, differences between the host and bacterial cell membranes exist, and these present potentially selective targets for HDPs. Several HDPs preferentially disrupt bacterial and cancer cell membranes rather than host eukaryotic cell membranes [77] and [78]. The cancer cell membranes contain a large amount of negatively charged PS, which is more negative than that of normal eukaryotic cells [79]. Therefore, it has been suggested that the increase in negatively charged PS in the cancer cell membranes makes them more susceptible to the cytotoxicity of the peptides than normal eukaryotic cells [80]. In addition, these peptides that disrupt target cell membranes as part of their killing effect show irreversible activity [81] and [82].