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A proapoptotic peptide conjugated to penetratin selectively inhibits tumor cell growth.

dc.rights.licenseopen
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorALVES, Isabel
hal.structure.identifierCentre de Recherches en Oncologie biologique et Oncopharmacologie [CRO2]
dc.contributor.authorCARRÉ, Manon
hal.structure.identifierCentre de Recherches en Oncologie biologique et Oncopharmacologie [CRO2]
dc.contributor.authorMONTERO, Marie-Pierre
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorCASTANO, Sabine
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLECOMTE, Sophie
hal.structure.identifierUniversité Pierre et Marie Curie - Paris 6 [UPMC]
dc.contributor.authorMARQUANT, Rodrigue
hal.structure.identifierUniversité Pierre et Marie Curie - Paris 6 [UPMC]
dc.contributor.authorLECORCHÉ, Pascaline
hal.structure.identifierUniversité Pierre et Marie Curie - Paris 6 [UPMC]
dc.contributor.authorBURLINA, Fabienne
hal.structure.identifierLaboratoire de Chimie des Polymères Organiques [LCPO]
hal.structure.identifierTeam 3 LCPO : Polymer Self-Assembly & Life Sciences
dc.contributor.authorSCHATZ, Christophe
hal.structure.identifierUniversité Pierre et Marie Curie - Paris 6 [UPMC]
dc.contributor.authorSAGAN, Sandrine
hal.structure.identifierUniversité Pierre et Marie Curie - Paris 6 [UPMC]
dc.contributor.authorCHASSAING, Gérard
hal.structure.identifierCentre de Recherches en Oncologie biologique et Oncopharmacologie [CRO2]
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorBRAGUER, Diane
hal.structure.identifierUniversité Pierre et Marie Curie - Paris 6 [UPMC]
dc.contributor.authorLAVIELLE, Solange
dc.date.accessioned2020
dc.date.available2020
dc.date.issued2014
dc.identifier.issn0006-3002
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/20319
dc.description.abstractEn: The peptide KLA (acetyl-(KLAKLAK)2-NH2), which is rather non toxic for eukaryotic cell lines, becomes active when coupled to the cell penetrating peptide, penetratin (Pen), by a disulfide bridge. Remarkably, the conjugate KLA-Pen is cytotoxic, at low micromolar concentrations, against a panel of seven human tumor cell lines of various tissue origins, including cells resistant to conventional chemotherapy agents but not to normal human cell lines. Live microscopy on cells possessing fluorescent labeled mitochondria shows that in tumor cells, KLA-Pen had a strong impact on mitochondria tubular organization instantly resulting in their aggregation, while the unconjugated KLA and pen peptides had no effect. But, mitochondria in various normal cells were not affected by KLA-Pen. The interaction with membrane models of KLA-Pen, KLA and penetratin were studied using dynamic light scattering, calorimetry, plasmon resonance, circular dichroism and ATR-FTIR to unveil the mode of action of the conjugate. To understand the selectivity of the conjugate towards tumor cell lines and its action on mitochondria, lipid model systems composed of zwitterionic lipids were used as mimics of normal cell membranes and anionic lipids as mimics of tumor cell and mitochondria membrane. A very distinct mode of interaction with the two model systems was observed. KLA-Pen may exert its deleterious and selective action on cancer cells by the formation of pores with an oblique membrane orientation and establishment of important hydrophobic interactions. These results suggest that KLA-Pen could be a lead compound for the design of cancer therapeutics.
dc.language.isoen
dc.publisherElsevier
dc.title.enA proapoptotic peptide conjugated to penetratin selectively inhibits tumor cell growth.
dc.typeArticle de revue
dc.identifier.doi10.1016/j.bbamem.2014.04.025
dc.subject.halChimie/Chimie organique
bordeaux.journalBBA - Biochimica et Biophysica Acta
bordeaux.page2087–2098
bordeaux.volume1838
bordeaux.hal.laboratoriesLaboratoire de Chimie des Polymères Organiques (LCPO) - UMR 5629*
bordeaux.issue8
bordeaux.institutionBordeaux INP
bordeaux.institutionUniversité de Bordeaux
bordeaux.peerReviewedoui
hal.identifierhal-00989572
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-00989572v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=BBA%20-%20Biochimica%20et%20Biophysica%20Acta&rft.date=2014&rft.volume=1838&rft.issue=8&rft.spage=2087%E2%80%932098&rft.epage=2087%E2%80%932098&rft.eissn=0006-3002&rft.issn=0006-3002&rft.au=ALVES,%20Isabel&CARR%C3%89,%20Manon&MONTERO,%20Marie-Pierre&CASTANO,%20Sabine&LECOMTE,%20Sophie&rft.genre=article


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