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dc.contributor.authorÜner, G.
dc.contributor.authorTag`, Ö.
dc.contributor.authorErzurumlu, Y.
dc.contributor.authorKirmizibayrak, P.B.
dc.contributor.authorBedir, E.
dc.date.accessioned2021-02-12T18:45:42Z
dc.date.available2021-02-12T18:45:42Z
dc.date.issued2020
dc.identifier.issn0893-228X
dc.identifier.urihttps://doi.org/10.1021/acs.chemrestox.0c00339
dc.identifier.urihttps://hdl.handle.net/11147/9927
dc.descriptionPubMed: 33136369en_US
dc.description.abstractSmall molecules which activate distinct cell death pathways have promising high potential for anticancer drug research. Especially, regulated necrosis draws attention as an alternative cell death mechanism to overcome the drug resistance. Here, we report that a new semisynthetic saponin analogue (AG-08) triggers necrotic cell death with unprecedented pathways. AG-08-mediated necrosis depends on enhanced global proteolysis involving calpains, cathepsins, and caspases. Moreover, AG-08 generates several alterations in lysosomal function and physiology including membrane permeabilization, redistribution toward the perinuclear area, and lastly excessive tubulation. As a consequence of lysosomal impairment, the autophagic process was abolished via AG-08 treatment. Collectively, in addition to its ability to induce necrotic cell death, which makes AG-08 a promising candidate to cope with drug resistance, its unique activity mechanisms including autophagy/lysosome impairment and enhancement of proteolysis leading a strong death capacity emphasizes its potential for anticancer drug research. ©en_US
dc.description.sponsorship118S709, 109S345 Türkiye Bilimsel ve Teknolojik Araştirma Kurumuen_US
dc.description.sponsorshipThis project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project No: 118S709) as a continuation of a prior project (TUBITAK, Project No: 109S345).en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.isversionof10.1021/acs.chemrestox.0c00339en_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.titleIdentification of a Noncanonical Necrotic Cell Death Triggered via Enhanced Proteolysis by a Novel Sapogenol Derivativeen_US
dc.typearticleen_US
dc.typearticleen_US
dc.relation.journalChemical Research in Toxicologyen_US
dc.contributor.departmentIzmir Isntitute of Technologyen_US
dc.identifier.volume33en_US
dc.identifier.issue11en_US
dc.identifier.startpage2880en_US
dc.identifier.endpage2891en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US


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