Four enantiomeric 9-mer
peptides named d-
peptide A, B, C and D were designed and synthesized on the basis of 43-mer insect
defensins from two beetles. The d-9-mer
peptides maintained bacterial membrane disruptive activity similar to the original
peptides and also showed various extents of growth inhibitory activity against different
cancer cell lines. Of these
peptides, d-
peptide B exhibited the highest selective
cancer cell cytotoxicity against the mouse myeloma cell line, P3-X63-Ag8.653. Flow cytometric and scanning electron microscopic analysis revealed d-
peptide B disrupts mouse myeloma membrane construction, whereas no cytotoxic effect on normal leukocytes was observed. Moreover, a strong correlation between negatively charged
phosphatidylserine (PS) density in
cancer cell membrane surface and sensitivity to d-9-mer
peptides were observed in various
cancer cell lines. These results suggest that d-9-mer
peptides have negative charge-dependent selective
cancer cell cytotoxicity targeting PS in the
cancer cell membrane. In addition, synergic growth inhibitory activity against mouse myeloma was observed in combinations of d-
peptide B and
dexamethasone. These results suggest d-9-mer
peptides are promising candidates for novel anticancer drugs.