Similarly, HDPs act via a non-receptor-mediated pathway against the target cell membranes as do melittin (a non-selective cytotoxic α-helical peptide), cecropin (a non-hemolytic α-helical peptide), and androctonin (a non-hemolytic β-sheeted peptide) [84] and [85]. Therefore, the biological activity shown 5-FU clinical trial by these peptides suggests the existence of killing mechanisms that involve

perturbation of the plasma membrane, inducing necrosis. Membrane-active peptides can induce the permeabilization of mitochondria, triggering apoptosis [82]. A cationic membrane-active antimicrobial peptide, CNGRC-GG-D(KLAKLAK)2, shows antitumor activity via the mitochondrial pathway of apoptosis [86]. Similarly, tachyplesin, a heptadecameric cationic antimicrobial peptide, could interact with the mitochondrial membranes of cancer cells and induce apoptosis [87] and [88].

www.selleckchem.com/products/gsk1120212-jtp-74057.html Thus, the cationic antimicrobial peptides exhibit antitumor activity. In the cathelicidin family, the bovine produced BMAP-27 and BMAP-28 have been shown to induce membrane permeabilization and apoptosis in human leukemic tumor cells and normal proliferating but not resting lymphocytes [89] and [90]. This is associated with cathelicidin peptide-induced membrane permeabilization and is followed by programmed cell death. This indicates that BMAP-28 induced mitochondrial membrane permeability and then caused mitochondrial depolarization and released cytochrome c, leading to apoptosis [90]. We have previously synthesized a 27-amino acid sequence from the C-terminal domain of hCAP18/LL-37 and described its antimicrobial activity against Porphyromonas and Prevotella species [62]. This peptide is designated hCAP18109–135 and consists of the active domain, as LL-37. In our recent study, hCAP18109–135 induced apoptotic cell death of squamous cell carcinoma cells, but not gingival fibroblasts or Carnitine palmitoyltransferase II normal keratinocytes and HaCaT cells [91]. The hCAP18109–135 induced apoptotic cell death was attributed to a caspase-independent

pathway ( Fig. 5, data unpublished). Furthermore, we demonstrated a correlation between different apoptotic events affecting the mitochondria, cytosol, and nuclei following hCAP18109–135 inductions. In order to examine the apoptotic effect of hCAP18109–135 on human squamous cell carcinoma SAS-H1 cells, the peptide was added at a concentration of 40 μg/ml in the presence of 10% fetal bovine serum. We showed that hCAP18109–135 elicited the translocation of Bax to the mitochondria and endonuclease G to the cytosol. Thus, in peptide-induced cell death, Bax-dependent endonuclease G release plays a role in caspase-independent oligonucleosomal DNA fragmentation ( Figure 6 and Figure 7, data unpublished).