title: Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis.
abstract: Harmoniasin is a defensin-like antimicrobial peptide identified from the ladybug Harmonia axyridis. Among the synthetic homodimer peptide analogues derived from harmoniasin, HaA4 has been found to have antibacterial activity without hemolytic activity. In this study, we investigated whether HaA4 has anticancer activity against human leukemia cell lines such as U937 and Jurkat cells. HaA4 manifested cytotoxicity and decreased the cell viability of U937 and Jurkat cells in MTS assay and LDH release assay. We found that HaA4 induced apoptotic and necrotic cell death of the leukemia cells using flow cytometric analysis, acridine orange/ethidium bromide staining and nucleosomal fragmentation of genomic DNA. Activation of caspase-7 and -9 and fragmentation of poly (ADP-ribose) polymerase was detected in the HaA4-treated leukemia cells, suggesting induction of a caspase-dependent apoptosis pathway by HaA4. Caspase-dependent apoptosis was further confirmed by reversal of the HaA4-induced viability reduction by treatment of Z-VAD-FMK, a pan-caspase inhibitor. In conclusion, HaA4 caused necrosis and caspase-dependent apoptosis in both U937 and Jurkat leukemia cells, which suggests potential utility of HaA4 as a cancer therapeutic agent.
authors.affiliation: Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon 441-853, Republic of Korea.
authors.forename: In-Woo
authors.initials: IW
authors.lastname: Kim
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Lee
authors.forename: Young-Nam
authors.initials: YN
authors.lastname: Kwon
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Yun
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Nam
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Ahn
authors.forename: Dong-Chul
authors.initials: DC
authors.lastname: Kang
authors.forename: Jae Sam
authors.initials: JS
authors.lastname: Hwang
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053179:Caspase 7 / Q000187:drug effects / Q000378:metabolism; D053453:Caspase 9 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019476:Insect Proteins / Q000494:pharmacology*; D019169:Jurkat Cells; D007938:Leukemia / Q000188:drug therapy; D051379:Mice; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D020298:U937 Cells
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; C587177:HaA4 peptide; D019476:Insect Proteins; D011065:Poly(ADP-ribose) Polymerases; D053179:Caspase 7; D053453:Caspase 9