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A Pyranoxanthone as a potent antimitotic and sensitizer of cancer cells to low doses of Paclitaxel

2020Journal article Open access
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dc.contributor.authorFrança, Fábio
dc.contributor.authorSilva, Patrícia M. A.
dc.contributor.authorSoares, José X.
dc.contributor.authorHenriques, Ana C.
dc.contributor.authorLoureiro, Daniela R. P.
dc.contributor.authorAzevedo, Carlos M. G.
dc.contributor.authorAfonso, Carlos M. M.
dc.contributor.authorBousbaa, Hassan
dc.date.accessioned2021-01-15T10:20:18Z
dc.date.available2021-01-15T10:20:18Z
dc.date.issued2020
dc.description.abstractMicrotubule-targeting agents (MTAs) remain a gold standard for the treatment of several cancer types. By interfering with microtubules dynamic, MTAs induce a mitotic arrest followed by cell death. This antimitotic activity of MTAs is dependent on the spindle assembly checkpoint (SAC), which monitors the integrity of the mitotic spindle and proper chromosome attachments to microtubules in order to ensure accurate chromosome segregation and timely anaphase onset. However, the cytotoxic activity of MTAs is restrained by drug resistance and/or toxicities, and had motivated the search for new compounds and/or alternative therapeutic strategies. Here, we describe the synthesis and mechanism of action of the xanthone derivative pyranoxanthone 2 that exhibits a potent anti-growth activity against cancer cells. We found that cancer cells treated with the pyranoxanthone 2 exhibited persistent defects in chromosome congression during mitosis that were not corrected over time, which induced a prolonged SAC-dependent mitotic arrest followed by massive apoptosis. Importantly, pyranoxanthone 2 was able to potentiate apoptosis of cancer cells treated with nanomolar concentrations of paclitaxel. Our data identified the potential of the pyranoxanthone 2 as a new potent antimitotic with promising antitumor potential, either alone or in combination regimens.pt_PT
dc.description.sponsorshipPortugal 2020: PTDC/SAU-PUB/28736/2017 (POCI-01-0145-FEDER-028736; FCT: SFRH/BD/116167/2016/ SFRH/BD/140844/2018/ PD/00016/2012pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3390/molecules25245845pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.1/14967
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationDevelopment of 2D optical array sensors based on the combined utilization of multiple luminescent quantum dots immobilized onto solid supports
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectPaclitaxelpt_PT
dc.subjectCancerpt_PT
dc.subjectPyranoxanthonept_PT
dc.subjectAntitumorpt_PT
dc.subjectMitosispt_PT
dc.subjectApoptosispt_PT
dc.titleA Pyranoxanthone as a potent antimitotic and sensitizer of cancer cells to low doses of Paclitaxelpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDevelopment of 2D optical array sensors based on the combined utilization of multiple luminescent quantum dots immobilized onto solid supports
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F98105%2F2013/PT
oaire.citation.issue24pt_PT
oaire.citation.startPage5845pt_PT
oaire.citation.titleMoleculespt_PT
oaire.citation.volume25pt_PT
person.familyNameFrança Vieira e Silva
person.givenNameFábio
person.identifier.ciencia-id6416-FFF9-3A87
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication6f9eb148-d81a-441a-b93a-63aec5e7e2de
relation.isAuthorOfPublication.latestForDiscovery6f9eb148-d81a-441a-b93a-63aec5e7e2de
relation.isProjectOfPublication574f05fb-cab8-41d5-bcdc-8db9916334a6
relation.isProjectOfPublication.latestForDiscovery574f05fb-cab8-41d5-bcdc-8db9916334a6

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