Cytotoxic activity of a tumor protease-activated pore-forming toxin. (Articolo in rivista)

Type
Label
  • Cytotoxic activity of a tumor protease-activated pore-forming toxin. (Articolo in rivista) (literal)
Anno
  • 2005-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1021/bc049873z (literal)
Alternative label
  • C. Potrich;*+ R. Tomazzolli;+ M. Dalla Serra;+ G. Anderluh;? P. Malovrh;? P. Macek;? G. Menestrina;+ and M.Tejuca+§ (2005)
    Cytotoxic activity of a tumor protease-activated pore-forming toxin.
    in Bioconjugate chemistry
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • C. Potrich;*+ R. Tomazzolli;+ M. Dalla Serra;+ G. Anderluh;? P. Malovrh;? P. Macek;? G. Menestrina;+ and M.Tejuca+§ (literal)
Pagina inizio
  • 369 (literal)
Pagina fine
  • 376 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 16 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 2 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • CNR-ITC Istituto di Biofisica Sezione di Trento, Via Sommarive 18, 38050 Povo (TN) Italy, Department of Biology, Biotechnical Faculty, University of Ljubljana, Vec?na pot 111, 1000 Ljubljana, Slovenia, and Departamento de Bioquimica, Facultad de Biologia, Universidad de la Habana, Calle 23 e/I y J, La Habana, Cuba. (literal)
Titolo
  • Cytotoxic activity of a tumor protease-activated pore-forming toxin. (literal)
Abstract
  • Equinatoxin II is a pore forming toxin produced by the sea anemone Actinia equina. It is able to kill very unspecifically most cell types by the membrane-perturbing action of an amphiphilic alpha-helix located at its N-terminal. A normally active N-terminal mutant, containing one single cys in the amphiphilic alpha-helix, becomes totally inactive when it is bound to avidin via a biotinylated linker. By choosing, as a linker, a peptide containing a tumor protease cleavage site, we were able to construct an enzymatically activable conjugate which should be selective for tumor cells. The introduced cleavage site was designed in order to be digested by both cathepsin B and matrix metalloproteases (MMPs). We confirmed that this conjugate could be activated in vitro by cathepsin B and MMPs. After having measured the enzymatic activity of fibrosarcoma and breast carcinoma cells, we analyzed the cytotoxic effect of the conjugate on the same lines and on human red blood cells (HRBC) as controls. We found that the conjugate was activated, at least in part, by the tumor cell lines used, whereas it was inactive on HRBC. That the activation process was dependent on the enzymatic action of cathepsin B and MMPs, was indicated by three lines of evidence: (1) binding occurred normally on all type of cells including HRBC which however were insensitive being devoid of enzymes; (2) the cytotoxic effect correlated with the amount of cathepsin B activity expressed by the cells; (3) conjugate activation was reduced by specific inhibitors of cathepsin B and MMPs. These results demonstrate the possibility of tumor cell killing by a pore-forming toxin conjugate specifically activated by tumor proteases. (literal)
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