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Metabolomics insights into doxorubicin and 5-fluorouracil combination therapy in triple-negative breast cancer: a xenograft mouse model study

2025-01-13Artigo científico Acesso aberto
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datacite.subject.fosCiências Naturais::Ciências Biológicas
dc.contributor.authorHassanein, Mai M.
dc.contributor.authorHagyousif, Yousra A.
dc.contributor.authorZenati, Ruba A.
dc.contributor.authorAl-Hroub, Hamza M.
dc.contributor.authorKhan, Farman Matloob
dc.contributor.authorAbuhelwa, Ahmad Y.
dc.contributor.authorAlzoubi, Karem H.
dc.contributor.authorSoares, Nelson C.
dc.contributor.authorEl-Huneidi, Waseem
dc.contributor.authorAbu-Gharbieh, Eman
dc.contributor.authorOmar, Hany
dc.contributor.authorZaher, Dana M.
dc.contributor.authorBustanji, Yasser
dc.contributor.authorSemreen, Mohammad H.
dc.date.accessioned2026-01-28T12:38:42Z
dc.date.available2026-01-28T12:38:42Z
dc.date.issued2025-01-13
dc.description.abstractBackground: Breast cancer is one of the most prevalent malignancies and a leading cause of death among women worldwide. Among its subtypes, triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive behavior and limited treatment options. This study aimed to investigate the effects of doxorubicin (DOX) and 5-fluorouracil (5-FU) as monotherapies and in combination using an established MDA-MB-231 xenograft model in female BALB/C nude mice employing advanced metabolomics analysis to identify molecular alterations induced by these treatments. Methods: We conducted comprehensive plasma and tumor tissue sample profiling using ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). Results: Each treatment group exhibited unique metabolic profiles in plasma and tumor analysis. Univariate and enrichment analyses identified alterations in metabolic pathways. The combination treatment of DOX + 5-FU induced the most extensive metabolic alterations disrupting key pathways including purine, pyrimidine, beta-alanine, and sphingolipid metabolism. It significantly reduced critical metabolites such as guanine, xanthine, inosine, L-fucose, and sphinganine, demonstrating enhanced cytotoxic effects compared to individual treatments. The DOX treatment uniquely increased ornithine levels, while 5-FU altered sphingolipid metabolism, promoting apoptosis. Significance: This in vivo study highlights TNBC's metabolic alterations to chemotherapeutics, identifying potential biomarkers like L-fucose and beta-alanine, and provides insights for improving treatment strategies.eng
dc.description.sponsorshipThis research was funded by University of Sharjah, Competitive grant No. 2201110155 and Targeted grant No. 24011101105 (MS).
dc.identifier.citationFront Mol Biosci. 2025 Jan 13:11:1517289. doi: 10.3389/fmolb.2024.1517289. eCollection 2024
dc.identifier.doi10.3389/fmolb.2024.1517289
dc.identifier.eissn2296-889X
dc.identifier.pmid39872164
dc.identifier.urihttp://hdl.handle.net/10400.18/10773
dc.language.isoeng
dc.peerreviewedyes
dc.publisherFrontiers Media
dc.relation.hasversionhttps://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1517289/full
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject5-flurouracil
dc.subjectMDA-MB-231 xenograft model
dc.subjectUHPLC-ESI-QTOF-MS
dc.subjectDoxorubicin
dc.subjectTriple-Negative Breast Cancer
dc.subjectuntargeted metabolomics analysis
dc.subjectDoenças Genéticas
dc.subjectGenómica Funcional e Estrutural
dc.titleMetabolomics insights into doxorubicin and 5-fluorouracil combination therapy in triple-negative breast cancer: a xenograft mouse model studyeng
dc.typejournal article
dcterms.referenceshttps://www.frontiersin.org/articles/10.3389/fmolb.2024.1517289/full#supplementary-material
dspace.entity.typePublication
oaire.citation.startPage1517289
oaire.citation.titleFrontiers in Molecular Biosciences
oaire.citation.volume11
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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