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Untargeted Multiomics of LNCaP Cell Line Treated with a Novel DNA Minor Groove Binder and/or Doxorubicin Using Mass Spectrometry

2025-09-04Artigo científico Acesso restrito
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datacite.subject.fosCiências Naturais::Ciências Biológicas
dc.contributor.authorZenati, Ruba A.
dc.contributor.authorSoares, Nelson C.
dc.contributor.authorAlniss, Hasan Y.
dc.contributor.authorAl-Hroub, Hamza M.
dc.contributor.authorEl-Awady, Raafat
dc.contributor.authorAbuhelwa, Ahmad Y.
dc.contributor.authorRamadan, Wafaa S.
dc.contributor.authorAleidi, Shereen M.
dc.contributor.authorEl-Huneidi, Waseem
dc.contributor.authorAbu-Gharbieh, Eman
dc.contributor.authorAlzoubi, Karem H.
dc.contributor.authorBustanji, Yasser
dc.contributor.authorSemreen, Mohammad H.
dc.date.accessioned2026-01-19T16:30:22Z
dc.date.available2026-01-19T16:30:22Z
dc.date.issued2025-09-04
dc.description.abstractProstate cancer (PCa) remains a major global health concern, ranking among the most prevalent cancer in men worldwide. Despite the availability of various therapeutic options, the clinical efficacy of current anti-PCa agents is often compromised by drug resistance and adverse effects. DNA minor groove binders offer a potential therapeutic alternative, owing to their selective mechanism of action and favorable safety profiles. In the present study, we utilized a multiomics strategy to investigate the molecular impact of novel compound MGB4. LNCaP cells were treated with doxorubicin, MGB4, or a combination of both, followed by LC-MS/MS-based untargeted proteomics and metabolomics analyses. One-way ANOVA (p-value <0.05) revealed 55 significantly dysregulated proteins and 57 altered metabolites across treatments. Our findings indicate that both MGB4 and doxorubicin impacted key cellular pathways, including inhibition of translation and alterations in sphingolipid and amino acid metabolism, while doxorubicin and the combination therapy also reduced spermine and spermidine metabolism. Notably, the combined treatment exhibited synergistic effects, significantly impacting purine metabolism and reducing metabolite levels more than individual therapies. This study provides key molecular insights into MGB4 and doxorubicin's mechanisms, supporting MGB4 as a potential prostate cancer drug candidate.eng
dc.description.sponsorshipThis study was financially supported by the University of Sharjah Targeted grant No. 24011101105 (M.H.S.).
dc.identifier.citationJ Proteome Res. 2025 Oct 3;24(10):4911-4924. doi: 10.1021/acs.jproteome.5c00135. Epub 2025 Sep 4
dc.identifier.doi10.1021/acs.jproteome.5c00135
dc.identifier.eissn1535-3907
dc.identifier.issn1535-3893
dc.identifier.urihttp://hdl.handle.net/10400.18/10715
dc.language.isoeng
dc.peerreviewedyes
dc.publisherAmerican Chemical Society
dc.relation.hasversionhttps://pubs.acs.org/doi/10.1021/acs.jproteome.5c00135
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectLC-MS/MS-QTOF
dc.subjectDoxorubicin
dc.subjectMetabolomics
dc.subjectProstate Cancer
dc.subjectProteomics
dc.subjectMinor Groove Binders (MGBs)
dc.subjectGenómica Funcional e Estrutural
dc.titleUntargeted Multiomics of LNCaP Cell Line Treated with a Novel DNA Minor Groove Binder and/or Doxorubicin Using Mass Spectrometryeng
dc.typejournal article
dcterms.referenceshttps://pubs.acs.org/doi/10.1021/acs.jproteome.5c00135?goto=supporting-info
dspace.entity.typePublication
oaire.citation.endPage4924
oaire.citation.issue10
oaire.citation.startPage4911
oaire.citation.titleJournal of Proteome Research
oaire.citation.volume24
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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