Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/108734
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Soares, Joana | - |
dc.contributor.author | Raimundo, Liliana | - |
dc.contributor.author | Pereira, Nuno A. L. | - |
dc.contributor.author | Monteiro, Ângelo | - |
dc.contributor.author | Gomes, Sara | - |
dc.contributor.author | Bessa, Cláudia | - |
dc.contributor.author | Pereira, Clara | - |
dc.contributor.author | Queiroz, Glória | - |
dc.contributor.author | Bisio, Alessandra | - |
dc.contributor.author | Fernandes, João | - |
dc.contributor.author | Gomes, Célia | - |
dc.contributor.author | Reis, Flávio | - |
dc.contributor.author | Gonçalves, Jorge | - |
dc.contributor.author | Inga, Alberto | - |
dc.contributor.author | Santos, Maria M. M. | - |
dc.contributor.author | Saraiva, Lucília | - |
dc.date.accessioned | 2023-09-11T10:39:31Z | - |
dc.date.available | 2023-09-11T10:39:31Z | - |
dc.date.issued | 2016-01-26 | - |
dc.identifier.issn | 1949-2553 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/108734 | - |
dc.description.abstract | Restoration of the p53 pathway, namely by reactivation of mutant (mut) p53, represents a valuable anticancer strategy. Herein, we report the identification of the enantiopure tryptophanol-derived oxazoloisoindolinone SLMP53-1 as a novel reactivator of wild-type (wt) and mut p53, using a yeast-based screening strategy. SLMP53-1 has a p53-dependent anti-proliferative activity in human wt and mut p53R280K-expressing tumor cells. Additionally, SLMP53-1 enhances p53 transcriptional activity and restores wt-like DNA binding ability to mut p53R280K. In wt/mut p53-expressing tumor cells, SLMP53-1 triggers p53 transcription-dependent and mitochondrial apoptotic pathways involving BAX, and wt/mut p53 mitochondrial translocation. SLMP53-1 inhibits the migration of wt/mut p53-expressing tumor cells, and it shows promising p53-dependent synergistic effects with conventional chemotherapeutics. In xenograft mice models, SLMP53-1 inhibits the growth of wt/mut p53-expressing tumors, but not of p53-null tumors, without apparent toxicity. Collectively, besides the potential use of SLMP53-1 as anticancer drug, the tryptophanol-derived oxazoloisoindolinone scaffold represents a promissing starting point for the development of effective p53-reactivating drugs. | pt |
dc.language.iso | eng | pt |
dc.publisher | Impact Journals | pt |
dc.relation | UID/Multi/04378/2013 (UCIBIO/REQUIMTE) | pt |
dc.relation | SFRH/BD/78971/2011 | pt |
dc.relation | PD/ BI/113926/2015) | pt |
dc.relation | SFRH/BD/96189/2013 | pt |
dc.relation | SFRH/BD/87109/2012 | pt |
dc.relation | IF Program (IF/00732/2013) | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | Tumor | pt |
dc.subject | p53 | pt |
dc.subject | mutant | pt |
dc.subject | tryptophanol-derived oxazoloisoindolinones | pt |
dc.subject | anticancer chemotherapy | pt |
dc.subject.mesh | Animals | pt |
dc.subject.mesh | Antineoplastic Agents | pt |
dc.subject.mesh | Apoptosis | pt |
dc.subject.mesh | Blotting, Western | pt |
dc.subject.mesh | Cell Movement | pt |
dc.subject.mesh | Cell Proliferation | pt |
dc.subject.mesh | Colonic Neoplasms | pt |
dc.subject.mesh | High-Throughput Screening Assays | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Immunoenzyme Techniques | pt |
dc.subject.mesh | Isoindoles | pt |
dc.subject.mesh | Mice | pt |
dc.subject.mesh | Mice, Inbred BALB C | pt |
dc.subject.mesh | Mice, Nude | pt |
dc.subject.mesh | Mutation | pt |
dc.subject.mesh | Oxazoles | pt |
dc.subject.mesh | Piperidones | pt |
dc.subject.mesh | RNA, Messenger | pt |
dc.subject.mesh | Rats | pt |
dc.subject.mesh | Rats, Wistar | pt |
dc.subject.mesh | Real-Time Polymerase Chain Reaction | pt |
dc.subject.mesh | Reverse Transcriptase Polymerase Chain Reaction | pt |
dc.subject.mesh | Small Molecule Libraries | pt |
dc.subject.mesh | Tryptophan | pt |
dc.subject.mesh | Tumor Cells, Cultured | pt |
dc.subject.mesh | Tumor Suppressor Protein p53 | pt |
dc.subject.mesh | Xenograft Model Antitumor Assays | pt |
dc.title | Reactivation of wild-type and mutant p53 by tryptophanolderived oxazoloisoindolinone SLMP53-1, a novel anticancer small-molecule | pt |
dc.type | article | - |
degois.publication.firstPage | 4326 | pt |
degois.publication.lastPage | 4343 | pt |
degois.publication.issue | 4 | pt |
degois.publication.title | Oncotarget | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.18632/oncotarget.6775 | pt |
degois.publication.volume | 7 | pt |
dc.date.embargo | 2016-01-26 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.researchunit | Centre for Earth and Space Research of the University of Coimbra | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-1663-3334 | - |
crisitem.author.orcid | 0000-0002-7497-4129 | - |
crisitem.author.orcid | 0000-0003-3401-9554 | - |
Appears in Collections: | I&D IBILI - Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais |
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Reactivation-of-wildtype-and-mutant-p53-by-tryptophanolderived-oxazoloisoindolinone-SLMP531-a-novel-anticancer-smallmoleculeOncotarget.pdf | 4.75 MB | Adobe PDF | View/Open |
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