title: Rapid cytotoxicity of antimicrobial peptide tempoprin-1CEa in breast cancer cells through membrane destruction and intracellular calcium mechanism.
abstract: Temporin-1CEa is an antimicrobial peptide isolated from the skin secretions of the Chinese brown frog (Rana chensinensis). We have previously reported the rapid and broad-spectrum anticancer activity of temporin-1CEa in vitro. However, the detailed mechanisms for temporin-1CEa-induced cancer cell death are still weakly understood. In the present study, the mechanisms of temporin-1CEa-induced rapid cytotoxicity on two human breast cancer cell lines, MDA-MB-231 and MCF-7, were investigated. The MTT assay and the LDH leakage assay indicated that one-hour of incubation with temporin-1CEa led to cytotoxicity in a dose-dependent manner. The morphological observation using electronic microscopes suggested that one-hour exposure of temporin-1CEa resulted in profound morphological changes in both MDA-MB-231 and MCF-7 cells. The membrane-disrupting property of temporin-1CEa was further characterized by induction of cell-surface exposure of phosphatidylserine, elevation of plasma membrane permeability and rapid depolarization of transmembrane potential. Moreover, temporin-1CEa evoked intracellular calcium ion and reactive oxygen species (ROS) elevations as well as collapse of mitochondrial membrane potential (Δφm). In summary, the present study indicates that temporin-1CEa triggers rapid cell death in breast cancer cells. This rapid cytotoxic activity might be mediated by both membrane destruction and intracellular calcium mechanism.
authors.affiliation: Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, China.
authors.forename: Che
authors.initials: C
authors.lastname: Wang
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Tian
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Hui-Bing
authors.initials: HB
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.forename: Qing-Zhu
authors.initials: QZ
authors.lastname: Yang
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Ma
authors.forename: De-Jing
authors.initials: DJ
authors.lastname: Shang
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects* / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; C582109:temporin-1CEa, Rana chensinensis; D002118:Calcium