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dc.creatorAlcolea-Devesa, V. (Verónica)-
dc.creatorKarelia, D.N. (Deepkamal N.)-
dc.creatorPandey, M.K. (Manoj K.)-
dc.creatorPlano-Amatriain, D. (Daniel)-
dc.creatorSingh, P. (Parvesh)-
dc.creatorPalop-Cubillo, J.A. (Juan Antonio)-
dc.creatorAmin, S. (Shantu)-
dc.creatorSanmartin-Grijalba, C. (Carmen)-
dc.creatorSharma, A.K. (Arun K.)-
dc.date.accessioned2022-03-02T08:41:04Z-
dc.date.available2022-03-02T08:41:04Z-
dc.date.issued2019-
dc.identifier.citationAlcolea-Devesa, V. (Verónica); Karelia, D.N. (Deepkamal N.); Pandey, M.K. (Manoj K.); et al. "Identification of a novel quinoxaline-isoselenourea targeting the STAT3 pathway as a potential melanoma therapeutic". International Journal of Molecular Sciences. 20 (3), 2019, 521es
dc.identifier.issn1422-0067-
dc.identifier.urihttps://hdl.handle.net/10171/62969-
dc.description.abstractThe prognosis for patients with metastatic melanoma remains very poor. Constitutive signal transducer and activator of transcription 3 (STAT3) activation has been correlated to metastasis, poor patient survival, larger tumor size, and acquired resistance against vemurafenib (PLX-4032), suggesting its potential as a molecular target. We recently designed a series of isoseleno- and isothio-urea derivatives of several biologically active heterocyclic scaffolds. The cytotoxic effects of lead isoseleno- and isothio-urea derivatives (compounds 1 and 3) were studied in a panel of five melanoma cell lines, including B-RAFV600E-mutant and wild-type (WT) cells. Compound 1 (IC50 range 0.8–3.8 µM) showed lower IC50 values than compound 3 (IC50 range 8.1–38.7 µM) and the mutant B-RAF specific inhibitor PLX-4032 (IC50 ranging from 0.4 to >50 µM), especially at a short treatment time (24 h). These effects were long-lasting, since melanoma cells did not recover their proliferative potential after 14 days of treatment. In addition, we confirmed that compound 1 induced cell death by apoptosis using Live-and-Dead, Annexin V, and Caspase3/7 apoptosis assays. Furthermore, compound 1 reduced the protein levels of STAT3 and its phosphorylation, as well as decreased the expression of STAT3-regulated genes involved in metastasis and survival, such as survivin and c-myc. Compound 1 also upregulated the cell cycle inhibitor p21. Docking studies further revealed the favorable binding of compound 1 with the SH2 domain of STAT3, suggesting it acts through STAT3 inhibition. Taken together, our results suggest that compound 1 induces apoptosis by means of the inhibition of the STAT3 pathway, non-specifically targeting both B-RAF-mutant and WT melanoma cells, with much higher cytotoxicity than the current therapeutic drug PLX-4032.es_ES
dc.description.sponsorshipThis research was funded by Caixa Foundation-UNED-Caja Navarra.es_ES
dc.language.isoenges_ES
dc.publisherMDPI AGes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectSeleniumes_ES
dc.subjectIsoselenoureaes_ES
dc.subjectMelanomaes_ES
dc.subjectSTAT3es_ES
dc.subjectApoptosises_ES
dc.titleIdentification of a novel quinoxaline-isoselenourea targeting the STAT3 pathway as a potential melanoma therapeutices_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.description.noteThis article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).es_ES
dc.identifier.doi10.3390/ijms20030521-
dadun.citation.number3es_ES
dadun.citation.publicationNameInternational Journal of Molecular Scienceses_ES
dadun.citation.startingPage521es_ES
dadun.citation.volume20es_ES

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