title: Anti-proliferative effect on a colon adenocarcinoma cell line exerted by a membrane disrupting antimicrobial peptide KL15.
abstract: The antimicrobial and anticancer activities of an antimicrobial peptide (AMP) KL15 obtained through in silico modification on the sequences of 2 previously identified bacteriocins m2163 and m2386 from Lactobacillus casei ATCC 334 by us have been studied. While significant bactericidal effect on the pathogenic bacteria Listeria, Escherichia, Bacillus, Staphylococcus, Enterococcus is exerted by KL15, the AMP can also kill 2 human adenocarcinoma cells SW480 and Caco-2 with measured IC50 as 50 μg/ml or 26.3 μM. However, the IC50 determined for KL15 on killing the normal human mammary epithelial cell H184B5F5/M10 is 150 μg/ml. The conformation of KL15 dissolved in 50% 2,2,2-trifluroroethanol or in 2 large unilamellar vesicle systems determined by circular dichroism spectroscopy appears to be helical. Further, the cell membrane permeability of treated SW480 cells by KL15 appears to be significantly enhanced as studied by both flow cytometry and confocal microscopy. As observed under a scanning electron microscope, the morphology of treated SW480 cells is also significantly changed as treating time by 80 μg/ml KL15 is increased. KL15 appears to be able to pierce the cell membrane of treated SW480 cells so that numerous porous structures are generated and observable. Therefore, KL15 is likely to kill the treated SW480 cells through the necrotic pathway similar to some recently identified AMPs by others.
authors.affiliation: a Institute of Molecular Medicine and Department of Life Science ; National Tsing Hua University ; HsinChu , Taiwan, R.O.C.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Tsai
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Ye
authors.forename: Thy-Hou
authors.initials: TH
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry; D018938:Caco-2 Cells / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002942:Circular Dichroism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003198:Computer Simulation; D006801:Humans; D020128:Inhibitory Concentration 50; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D011487:Protein Conformation; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; C000607364:KL15 peptide; C000600024:antimicrobial peptide m2163, Lactobacillus casei; C000600025:antimicrobial peptide m2386, Lactobacillus casei; D010767:Phosphorylcholine; D012967:Sodium Dodecyl Sulfate; C028810:dodecylphosphocholine
keywords: ABC, ATB-binding cassette; HFFF, human foetal foreskin fibroblast; HNSCC, head and neck squamous cell carcinoma; HPK, histidine protein kinase; MTT, 3-(4 5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; PS, phospholipid phosphatidylyserine; TFE, 2,2,2-trifluoroethanol; anticancer; antimicrobial; antiproliferation; apoptotic; membrane permeability; necrotic; peptide