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Intrinsic Proteolytic Activities from Cancer Cells Are Sufficient to Activate Alkoxyamine Prodrugs and Induce Cell Death

dc.rights.licenseopenen_US
dc.contributor.authorFILLIÂTRE, Marion
dc.contributor.authorSEREN, Seda
dc.contributor.authorEMBO-IBOUANGA, Ange
dc.contributor.authorJOLY, Jean-Patrick
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorBOUCHAUD, Véronique
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorKELKOUL, Ines
dc.contributor.authorMARQUE, Sylvain
dc.contributor.authorAUDRAN, Gérard
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorVOISIN, Pierre
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorMELLET, Philippe
dc.date.accessioned2024-11-14T12:34:33Z
dc.date.available2024-11-14T12:34:33Z
dc.date.issued2024-09-05
dc.identifier.issn2470-1343en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/203267
dc.description.abstractEnIn search of better specificity and lower chances of resistance, protease-activatable alkoxyamine prodrugs to fight cancer have been proposed. These molecules are made of a peptide linked to an alkoxyamine. Proteolysis of the peptide converts the stable prodrug at 37 °C to a metastable alkoxyamine that spontaneously homolyzes into two free radicals: a stable nitroxide and a very reactive alkyl radical. The alkyl radical induces apoptosis in the surrounding cells by inducing random chemical alterations. Here, we show that varying the peptide moiety from succinyl-Ala-Ala-Pro-Val- to PyroGlu-Gly-Arg- or PyroGlu-Gly-Lys- is effective in switching the activating enzyme from elastase to urokinase. Furthermore, these prodrugs induce the death of HT-1080 cells, a cell line that secretes several active proteases in culture. This cytotoxic activity can be suppressed by protease inhibitors and does not affect cell lines devoid of active urokinase. We thus provide examples of alkoxyamine prodrugs that are efficiently activated by the limited intrinsic protease activity and that succeed in the destruction of cancer cell lines and cancer cells from tumor explants.
dc.language.isoENen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/
dc.title.enIntrinsic Proteolytic Activities from Cancer Cells Are Sufficient to Activate Alkoxyamine Prodrugs and Induce Cell Death
dc.title.alternativeACS Omegaen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1021/acsomega.4c05592en_US
dc.subject.halSciences du Vivant [q-bio]en_US
dc.identifier.pubmed39310132en_US
bordeaux.journalACS Omegaen_US
bordeaux.page39004-39012en_US
bordeaux.volume9en_US
bordeaux.hal.laboratoriesCentre de Résonance Magnétique des Systèmes Biologiques (CRMSB) - UMR 5536en_US
bordeaux.issue37en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-04765968
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=ACS%20Omega&rft.date=2024-09-05&rft.volume=9&rft.issue=37&rft.spage=39004-39012&rft.epage=39004-39012&rft.eissn=2470-1343&rft.issn=2470-1343&rft.au=FILLI%C3%82TRE,%20Marion&SEREN,%20Seda&EMBO-IBOUANGA,%20Ange&JOLY,%20Jean-Patrick&BOUCHAUD,%20V%C3%A9ronique&rft.genre=article


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