title: Certain protein transducing agents convert translocated proteins into cell killers.
abstract: The majority of proteins are unable to translocate into the cell interior. Hence for peptide- and protein-based therapeutics a direct intracytoplasmic delivery with the aid of transducing agents is an attractive approach. We wanted to deliver to the cell interior a putatively cytotoxic protein VPg. Protein transduction was achieved in vitro with three different commercial products. However, in our hands, delivery of various control proteins without known deleterious effects, as well as of protein VPg, always induced cell death. Finally, we used a novel transducing peptide Wr-T, which was not toxic to cultured cells, even in a quite large range of concentrations. Most importantly, control protein delivered to cells in culture did not display any toxicity while VPg protein exerted a strong cytotoxic effect. These data show that results obtained with cell-penetrating agents should be interpreted with caution.
authors.affiliation: Institute of Structural Biology, CNRS-CEA-UJF, UMR, Grenoble, France.
authors.forename: Siergiej
authors.initials: S
authors.lastname: Tcherniuk
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Fiser
authors.forename: Madiha
authors.initials: M
authors.lastname: Derouazi
authors.forename: Bertrand
authors.initials: B
authors.lastname: Toussaint
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Izabela
authors.initials: I
authors.lastname: Wojtal
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.forename: Ewa
authors.initials: E
authors.lastname: Szolajska
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Chroboczek
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D016923:Cell Death; D049109:Cell Proliferation; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D016503:Drug Delivery Systems / Q000379:methods / Q000592:standards; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D013997:Time Factors; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D016895:Culture Media, Serum-Free; D010455:Peptides; D014764:Viral Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D007770:L-Lactate Dehydrogenase