title: In vitro Characterization of the Rapid Cytotoxicity of Anticancer Peptide HPRP-A2 through Membrane Destruction and Intracellular Mechanism against Gastric Cancer Cell Lines.
abstract: In this study, HPRP-A2, a synthetic 15-mer cationic peptides with all D-amino acids, effectively inhibited the survival of gastric cell lines in a dose-dependent manner. Gastric tumor cells killing by HPRP-A2 involves a rapid collapse of the membrane integrity and intracellular pathways. Propidium iodide (PI) and lactate dehydrogenase (LDH) assays demonstrated that one-hour treatment with HPRP-A2 led to membrane permeability changes of BGC-823 cells in a dose-dependent manner. Moreover, HPRP-A2 induced apoptosis in BGC-823 cells involves a marked increase in generation of reactive oxygen species (ROS),caspase-3, -8 and -9 activation, a reduction of mitochondrial membrane potential (MMP), and cell cycle arrest in G1 phase. In addition to its inherent cytotoxicity, HPRP-A2 synergized strongly with doxorubicin (DOX) to enhance the efficacy of killing gastric tumor cells in vitro. We believe that HPRP-A2 with all D-amino acids could be a potent candidate of anticancer therapeutics, especially in combination therapy.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China; School of Life Sciences, Jilin University, Changchun, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China; School of Life Sciences, Jilin University, Changchun, China.
authors.forename: Xueyu
authors.initials: X
authors.lastname: Hao
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China; School of Life Sciences, Jilin University, Changchun, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China; School of Life Sciences, Jilin University, Changchun, China; National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China; School of Life Sciences, Jilin University, Changchun, China; National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy*
chemical_list: D010455:Peptides; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D020169:Caspases