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dc.contributor.advisorPeterson-Peguero, Esther A
dc.contributor.authorRodriguez-Martir, Keishla M
dc.date.accessioned2022-06-29T21:46:11Z
dc.date.available2022-06-29T21:46:11Z
dc.date.issued2022-05-25
dc.identifier.urihttps://hdl.handle.net/11721/2854
dc.description.abstractCoumestrol (Cou) is a phytoestrogen present in soy and clover sprouts which is structurally similar to estrogen (E2) and has a cytotoxic effect in breast cancer cell lines. Nevertheless, the molecular mechanism by which Cou can exert its effect in the most aggressive breast cancer subtype, triple-negative inflammatory breast cancer (TN-IBC), is still unknown. Studies show that TN-IBC cell lines are unresponsive to hormonal therapies, but E2 can activate signaling pathways involved in pro-oncogenic phenotypes such as motility and invasion by activating a rapid estrogen-dependent non-genomic signaling. Therefore, the objective of this study was to determine the anti-cancer effect of Cou in TN-IBC cell lines (using 2D and 3D culture models) and the molecular mechanism Cou exerts for its anti-cancer activity. Dose-response curves of Cou in 2D and 3D culture models of TN-IBC cell lines were generated to determine the half-maximal inhibitory concentration (IC<sub>50</sub>). Relative cell viability was measured in ER-positive, triple-negative, TN-IBC, and HER2-amplified IBC cell lines. Functional assays were performed in TN-IBC cell lines to determine the effect of E2, Cou, and E2/Cou combination treatments on cell viability, migration, invasion, proliferation, and tumor emboli growth. Additionally, the effect of Cou and E2 treatments on phosphorylation of downstream kinases was analyzed by a proteome profile human phospho-kinase array. RNA-seq was performed in TN-IBC cell lines to identify transcriptome changes after Cou treatment. Our data demonstrated that Cou treatment using the IC<sub>50</sub> (13&micro;M in 2D models and 50&micro;M in 3D models) decreased cell viability in TN-IBC cell lines. Similarly, Cou treatment reduces triple-negative non-IBC cell viability. In comparison with E2, Cou decreases migration, invasion, proliferation, and tumor emboli growth in TN-IBC cell lines. Finally, Cou treatment reduces the phosphorylation of kinases MAPK/ERK and PI3K/AKT that promote pro-oncogenic phenotypes and upregulate genes such as TIPARP, recently involved in breast cancer phenotype suppression. In summary, this study guide us in elucidating a signaling pathway affected by Cou&rsquo;s anti-cancer activity. More importantly, it opens the opportunities to design more effective targeted therapeutic strategies to improve the prognosis and survival rates of IBC patients.en_US
dc.description.sponsorshipThis project is supported by UPR Fondos Institucionales para la Investigación (FIPI to E. Peterson), NIH 1R21CA253609-01 and RISE program (5R25GM061151-20).en_US
dc.language.isoen_USen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectAnticancer agenten_US
dc.subjectEstrogen non-genomic signaling pathwayen_US
dc.subjectInflammatory breast cáncer (IBC)en_US
dc.subject.lcshBreast--Canceren_US
dc.subject.lcshCancer--Treatmenten_US
dc.subject.lcshCoumestrolen_US
dc.subject.lcshInflammatory disease and therapyen_US
dc.subject.lcshPhytoestrogensen_US
dc.titlePhytoestrogen coumestrol as an anti-cancer therapy against triple-negative inflammatory breast canceren_US
dc.typeDissertationen_US
dc.rights.holder© 2022 Keishla M. Rodriguez-Martiren_US
dc.contributor.committeeZayas, Beatriz
dc.contributor.committeeVivas, Pablo
dc.contributor.committeeAgosto, José
dc.contributor.committeeRodriguez-Martinez, José A
dc.contributor.campusUniversity of Puerto Rico, Río Piedras Campusen_US
dc.description.graduationSemesterSpring (2nd Semester)en_US
dc.description.graduationYear2022en_US
thesis.degree.disciplineBiologyen_US
thesis.degree.levelPh.D.en_US


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Attribution-NonCommercial-NoDerivs 3.0 United States
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 United States