title: Novel cytotoxic exhibition mode of antimicrobial peptide anoplin in MEL cells, the cell line of murine Friend leukemia virus-induced leukemic cells.
abstract: Anoplin is a recently discovered antimicrobial peptide (AMP) isolated from the venom sac of the spider wasp Anoplius samariensis, and it is one of the shortest α-helical AMP found naturally to date consisting of only ten amino acids. Previous results showed that anoplin exhibits potent antimicrobial activity but little hemolytic activity. In this study, we synthesized anoplin, studied its cytotoxicity in Friend virus-induced leukemia cells [murine erythroleukemia (MEL) cells], and proposed its possible mechanism. Our results showed that anoplin could inhibit the proliferation of MEL cells in a dose-dependent and time-dependent manner via disrupting the integrity of cell membrane, which indicated that anoplin exerts its cytotoxicity efficacy. In addition, the cell cycle distribution of MEL cells was arrested in the G₀/G₁ phase significantly. However, anoplin could not induce obvious apoptosis in MEL cells, as well as anoplin could not induce visible changes on morphology and quantity in the bone marrow cells isolated from normal mice. All of these results indicate that anoplin, as generally believed, is a selective AMP, a value characteristic in the design of safe therapeutic agents. The cytotoxicity of anoplin on MEL cells was mainly attributable to the plasma membrane perturbation and also to the intracellular events such as the arrest of cell cycle. Although this is an initial study that explored the activity of anoplin in vitro rather than in vivo, with the increasing resistance of conventional chemotherapy, there is no doubt that anoplin has desirable feature to be developed as a novel and selective anticancer agent.
authors.affiliation: Lab of Proteomics & Molecular Enzymology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Zhu
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Fu
authors.forename: Shi-Fu
authors.initials: SF
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Yuan-Ting
authors.initials: YT
authors.lastname: Jin
authors.forename: Fu-Kun
authors.initials: FK
authors.lastname: Zhao
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005622:Friend murine leukemia virus; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000821:virology; D051379:Mice; D014862:Wasp Venoms / Q000494:pharmacology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D014862:Wasp Venoms; C443041:anoplin
keywords: Friend virus-induced leukemia cells; anoplin; apoptosis; cell cycle distribution; plasma membrane perturbation