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dc.contributor.authorMattiolo, Paolo
dc.contributor.authorBarbero-Farran A.
dc.contributor.authorAmigó J.
dc.contributor.authorRipamonti M.
dc.contributor.authorRibas i Fortuny, Judit
dc.contributor.authorBoix Torras, Jacint
dc.date.accessioned2015-02-03T16:38:03Z
dc.date.available2015-02-03T16:38:03Z
dc.date.issued2014
dc.identifier.issn0304-3835
dc.identifier.urihttp://hdl.handle.net/10459.1/47849
dc.description.abstractPES (2-phenylethynesulfonamide) was initially identified as an inhibitor of p53 translocation to mitochondria and named Pifithrin-µ. Further studies showed that PES selectively killed tumour cells and was thus a promising anticancer agent. PES-induced cell death was characterised by a non-apoptotic, autophagosome-rich phenotype. We observed this phenotype via electron microscopy in wild type (wt) and double Bax-/- Bak-/- (DKO) mouse embryonic fibroblasts (MEFs) treated with PES. We excluded the involvement of effector caspases, BAX and BAK, in causing PES-triggered cell death. Therefore, apoptosis was ruled out as the lethal mode of action of PES. Surprisingly, MEFs containing BAX were significantly protected from PES treatments. BAX overexpression in Bax-/- MEFs confirmed this pro-survival effect. Moreover, this protective effect required the ability of BAX to localise to mitochondrial membranes. Conversely, mitochondrial fusion induced by treatment with Mdivi-1 conferred increased resistance to MEFs subjected to PES treatment. The involvement of BAX in the regulation of mitochondrial dynamics has been reported. We propose the promotion of mitochondrial fusion by BAX to be the pro-survival function attributed to BAX.
dc.description.sponsorshipThis work was supported by the Spanish Government, MINECO (Ministerio de Economía y Competitividad), project SAF2011-29730. Paolo Mattiolo was supported by an FI fellowship from AGAUR (Generalitat de Catalunya).
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherElsevier
dc.relationMICINN/PN2008-2011/SAF2011-29730
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1016/j.canlet.2014.07.037
dc.relation.ispartofCancer Letters, 2014, vol. 354, num. 1, p. 115-121
dc.rights(c) Elsevier Ireland, 2014
dc.subjectPES (2-phenylethynesulfonamide)
dc.subjectpifithrin-mu
dc.subjectmitochondrial dynamics
dc.subjectBcl-2
dc.subjectNecrosis
dc.subject.classificationMitocondris
dc.subject.classificationMort cel·lular
dc.subject.otherMitochondria
dc.subject.otherCell death
dc.titleCell death induced by 2-phenylethynesulfonamide uncovers a pro-survival function of BAX
dc.typeinfo:eu-repo/semantics/article
dc.identifier.idgrec021380
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1016/j.canlet.2014.07.037


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