title: Selective cytotoxicity of the antibacterial peptide ABP-dHC-Cecropin A and its analog towards leukemia cells.
abstract: Some cationic antibacterial peptides, with typical amphiphilic α-helical conformations in a membrane-mimicking environment, exhibit anticancer properties as a result of a similar mechanism of action towards both bacteria and cancer cells. We previously reported the cDNA sequence of the antimicrobial peptide ABP-dHC-Cecropin A precursor cloned from drury (Hyphantria cunea) (dHC). In the present study, we synthesized and structurally characterized ABP-dHC-Cecropin A and its analog, ABP-dHC-Cecropin A-K(24). Circular dichroism spectroscopy showed that ABP-dHC-Cecropin A and its analog adopt a well-defined α-helical structure in a 50% trifluorethanol solution. The cytotoxicity and cell selectivity of these peptides were further examined in three leukemia cell lines and two non-cancerous cell lines. The MTT assay indicated both of these peptides have a concentration-dependent cytotoxic effect in leukemia cells, although the observed cytotoxicity was greater with ABP-dHC-Cecropin A-K(24) treatment, whereas they were not cytotoxic towards the non-cancerous cell lines. Moreover, ABP-dHC-Cecropin A and its analog had a lower hemolytic effect in human red blood cells. Together, these results suggest the peptides are selectively cytotoxic towards leukemia cells. Confocal laser scanning microscopy determined that the peptides were concentrated at the surface of the leukemia cells, and changes in the cell membrane were determined with a permeability assay, which suggested that the anticancer activity of ABP-dHC-Cecropin A and its analog is a result of its presence at the leukemia cell membrane. ABP-dHC-Cecropin A and its analog may represent a novel anticancer agent for leukemia therapy, considering its cancer cell selectivity and relatively low cytotoxicity in normal cells.
authors.affiliation: Co-Innovation Center for Sustainable Forestry in Southern China, Key Laboratory of Forest Genetics & Biotechnology, Ministry of Education, Nanjing Forestry University, Nanjing 210037, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sang
authors.affiliation: Co-Innovation Center for Sustainable Forestry in Southern China, Key Laboratory of Forest Genetics & Biotechnology, Ministry of Education, Nanjing Forestry University, Nanjing 210037, China. Electronic address: zhangjiaxin60633@163.com.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Co-Innovation Center for Sustainable Forestry in Southern China, Key Laboratory of Forest Genetics & Biotechnology, Ministry of Education, Nanjing Forestry University, Nanjing 210037, China. Electronic address: qzhuge@njfu.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhuge
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007938:Leukemia / Q000473:pathology*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; C031161:cecropin A
keywords: ABP-dHC-Cecropin A; Antibacterial peptide; Anticancer peptide; Cytotoxicity; Selectivity