Lipopolyamine treatment increases the efficacy of intoxication with saporin and an anticancer saporin conjugate (Articolo in rivista)

Type
Label
  • Lipopolyamine treatment increases the efficacy of intoxication with saporin and an anticancer saporin conjugate (Articolo in rivista) (literal)
Anno
  • 2007-01-01T00:00:00+01:00 (literal)
Alternative label
  • Geden S.E., Gardner R.A., Fabbrini M.S., Ohashi M., Phanstiel Iv O., Teter K. (2007)
    Lipopolyamine treatment increases the efficacy of intoxication with saporin and an anticancer saporin conjugate
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Geden S.E., Gardner R.A., Fabbrini M.S., Ohashi M., Phanstiel Iv O., Teter K. (literal)
Pagina inizio
  • 4825 (literal)
Pagina fine
  • 4836 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni
  • Pensiamo che l’uso di questi composti possa essere integrato nelle terapie antitumorali basate su chimere con Saporina per potenziarne gli effetti (literal)
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  • 274 (literal)
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  • Continuazione di “ European Journal of Biochemistry “, FEBS Journal è una rivista con un fattore d'impatto 3.579 (2006) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#descrizioneSinteticaDelProdotto
  • Pubblicazione scientifica riguardante l'utilizzo di lipopoliammine o di uno shock con dimetilsolfossido per sensibilizzare le cellule bersaglio alla tossina di pianta saporina da Saponaria officinalis e ad un suo coniugato antimetastatico con urochinasi. Si mostra anche che lo step di sensibilizazione avviene dopo internalizzazione probabilmente grazie alla permeabilizzazione degli endosomi “early” e si mostra che la via di intossicazione di Saporina passa attraverso questi comparti intracellulari anche grazie all’utilizzo di mutanti in cellule CHO LEX1 e LEX2 (deficienti nel trasporto dagli endosomi ai lisosomi ) che sono risultati significativamente più sensibili a saporina rispetto alle cellule parentali di controllo. (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • GSE,TK- Department of Molecular Biology and Microbiology and Biomolecular Science Center, University of Central Florida, FL, USA; GRA,PIv- Department of Chemistry and Biomolecular Science Center, University of Central Florida, FL, USA; FMS- Istituto Biologia e Biotecnologia Agraria, CNR, Milan, Italy; OM- Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Japan) (literal)
Titolo
  • Lipopolyamine treatment increases the efficacy of intoxication with saporin and an anticancer saporin conjugate (literal)
Abstract
  • Saporin is a type I ribosome-inactivating protein that is often appended with a cell-binding domain to specifically target and kill cancer cells. Urokinase plasminogen activator (uPA)-saporin, for example, is an anticancer toxin that consists of a chemical conjugate between the human uPA and native saporin. Both saporin and uPA-saporin enter the target cell by endocytosis and must then escape the endomembrane system to reach the cytosolic ribosomes. The latter process may represent a rate-limiting step for intoxication and would therefore directly affect toxin potency. In the present study, we document two treatments (shock with dimethylsulfoxide and lipopolyamine coadministration) that generate substantial cellular sensitization to saporin D uPA-saporin. With the use of lysosome-endosome X (LEX)1 and LEX2 mutant cell lines, an endosomal trafficking step preceding cargo delivery to the late endosomes was identified as a major site for the dimethylsulfoxide-facilitated entry of saporin into the cytosol. Dimethylsulfoxide and lipopolyamines are known to disrupt the integrity of endosome membranes, so these reagents could facilitate the rapid movement of toxin from permeabilized endosomes to the cytosol. However, the same pattern of toxin sensitization was not observed for dimethylsulfoxide- or lipopolyamine-treated cells exposed to diphtheria toxin, ricin, or the catalytic A chain of ricin. The sensitization effects were thus specific for saporin, suggesting a novel mechanism of saporin translocation by endosome disruption. Lipopolyamines have been developed as in vivo gene therapy vectors; thus, lipopolyamine coadministration with uPA-saporin or other saporin conjugates could represent a new approach for anticancer toxin treatments. (literal)
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