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dc.contributor.authorEike, Liv-Marie
dc.contributor.authorYang, Nannan
dc.contributor.authorRekdal, Øystein
dc.contributor.authorSveinbjørnsson, Baldur
dc.date.accessioned2016-03-04T10:07:23Z
dc.date.available2016-03-04T10:07:23Z
dc.date.issued2015-10-13
dc.description.abstractHost defense peptides (HDPs) are naturally occurring molecules found in most species, in which they play a significant role in the first line defense against intruding pathogens, and several HDPs have been shown to possess anticancer activity. Structure-activity relationship studies on the HDP bovine lactoferricin revealed a de novo design of a nonamer peptide LTX-315, with oncolytic properties. In the present study, we investigated the oncolytic activity of LTX-315 in human melanoma cells (A375). LTX-315 induced a rapid plasma membrane disruption and cell death within 2 hours. At a low concentration, fluorescence-labeled LTX-315 was internalized and accumulated in cytoplasmic vacuoles in close proximity to the mitochondria. The mitochondrial membrane potential was shown to depolarize as a consequence of LTX-315 treatment and at ultrastructural level, the mitochondria morphology was significantly altered. Release of danger signals (DAMPs) such as ATP, Cytochrome C and HMGB1 into the cell supernatant of cultured cells was evident minutes after peptide treatment. The oncolytic effect of LTX-315 involving perturbation of both the cell membrane and the mitochondria with subsequent release of DAMPs may highlight the ability of LTX-315 to induce complete regression and long-term protective immune responses as previously reported in experimental animal models.en_US
dc.identifier.citationOncoTarget 2015, 6(33):34910-34923en_US
dc.identifier.cristinIDFRIDAID 1292242
dc.identifier.doi10.18632/oncotarget.5308
dc.identifier.issn1949-2553
dc.identifier.urihttps://hdl.handle.net/10037/8679
dc.identifier.urnURN:NBN:no-uit_munin_8182
dc.language.isoengen_US
dc.publisherImpact Journalsen_US
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi: 711en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical molecular biology: 711en_US
dc.titleThe oncolytic peptide LTX-315 induces cell death and DAMP release by mitochondria distortion in human melanoma cellsen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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