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dc.contributor.authorRajasekaran, Devarajaen_US
dc.contributor.authorSiddiq, Ayeshaen_US
dc.contributor.authorWilloughby, Jennifer L. S.en_US
dc.contributor.authorBiagi, Jessica M.en_US
dc.contributor.authorChristadore, Lisa M.en_US
dc.contributor.authorYunes, Sarah A.en_US
dc.contributor.authorGredler, Rachelen_US
dc.contributor.authorJariwala, Nidhien_US
dc.contributor.authorRobertson, Chadia L.en_US
dc.contributor.authorAkiel, Maaged A.en_US
dc.contributor.authorShen, Xue-Ningen_US
dc.contributor.authorSubler, Mark A.en_US
dc.contributor.authorWindle, Jolene J.en_US
dc.contributor.authorSchaus, Scott E.en_US
dc.contributor.authorFisher, Paul B.en_US
dc.contributor.authorHansen, Ullaen_US
dc.contributor.authorSarkar, Devananden_US
dc.date.accessioned2020-05-01T20:51:10Z
dc.date.available2020-05-01T20:51:10Z
dc.date.issued2015-09-22
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000363160100129&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e74115fe3da270499c3d65c9b17d654
dc.identifier.citationDevaraja Rajasekaran, Ayesha Siddiq, Jennifer LS Willoughby, Jessica M Biagi, Lisa M Christadore, Sarah A Yunes, Rachel Gredler, Nidhi Jariwala, Chadia L Robertson, Maaged A Akiel, Xue-Ning Shen, Mark A Subler, Jolene J Windle, Scott E Schaus, Paul B Fisher, Ulla Hansen, Devanand Sarkar. 2015. "Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): Evaluation using an endogenous HCC model." ONCOTARGET, Volume 6, Issue 28, pp. 26266 - 26277 (12). https://doi.org/10.18632/oncotarget.4656
dc.identifier.issn1949-2553
dc.identifier.urihttps://hdl.handle.net/2144/40516
dc.description.abstractHepatocellular carcinoma (HCC) is a lethal malignancy with high mortality and poor prognosis. Oncogenic transcription factor Late SV40 Factor (LSF) plays an important role in promoting HCC. A small molecule inhibitor of LSF, Factor Quinolinone Inhibitor 1 (FQI1), significantly inhibited human HCC xenografts in nude mice without harming normal cells. Here we evaluated the efficacy of FQI1 and another inhibitor, FQI2, in inhibiting endogenous hepatocarcinogenesis. HCC was induced in a transgenic mouse with hepatocyte-specific overexpression of c-myc (Alb/c-myc) by injecting N-nitrosodiethylamine (DEN) followed by FQI1 or FQI2 treatment after tumor development. LSF inhibitors markedly decreased tumor burden in Alb/c-myc mice with a corresponding decrease in proliferation and angiogenesis. Interestingly, in vitro treatment of human HCC cells with LSF inhibitors resulted in mitotic arrest with an accompanying increase in CyclinB1. Inhibition of CyclinB1 induction by Cycloheximide or CDK1 activity by Roscovitine significantly prevented FQI-induced mitotic arrest. A significant induction of apoptosis was also observed upon treatment with FQI. These effects of LSF inhibition, mitotic arrest and induction of apoptosis by FQI1s provide multiple avenues by which these inhibitors eliminate HCC cells. LSF inhibitors might be highly potent and effective therapeutics for HCC either alone or in combination with currently existing therapies.en_US
dc.description.sponsorshipThe present study was supported in part by grants from The James S. McDonnell Foundation, National Cancer Institute Grant R01 CA138540-01A1 (DS), National Institutes of Health Grant R01 CA134721 (PBF), the Samuel Waxman Cancer Research Foundation (SWCRF) (DS and PBF), National Institutes of Health Grants R01 GM078240 and P50 GM67041 (SES), the Johnson and Johnson Clinical Innovation Award (UH), and the Boston University Ignition Award (UH). JLSW was supported by Alnylam Pharmaceuticals, Inc. DS is the Harrison Endowed Scholar in Cancer Research and Blick scholar. PBF holds the Thelma Newmeyer Corman Chair in Cancer Research. The authors acknowledge Dr. Lauren E. Brown (Dept. Chemistry, Boston University) for the synthesis of FQI1 and FQI2, and Lucy Flynn (Dept. Biology, Boston University) for initially identifying G2/M effects caused by FQI1. (James S. McDonnell Foundation; R01 CA138540-01A1 - National Cancer Institute; R01 CA134721 - National Institutes of Health; R01 GM078240 - National Institutes of Health; P50 GM67041 - National Institutes of Health; Samuel Waxman Cancer Research Foundation (SWCRF); Johnson and Johnson Clinical Innovation Award; Boston University Ignition Award; Alnylam Pharmaceuticals, Inc.)en_US
dc.format.extentp. 26266 - 26277en_US
dc.languageEnglish
dc.language.isoen_US
dc.publisherIMPACT JOURNALS LLCen_US
dc.relation.ispartofONCOTARGET
dc.rightsThis article is made available under a Creative Commons Attribution 3.0 License.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.subjectScience & technologyen_US
dc.subjectLife sciences & biomedicineen_US
dc.subjectOncologyen_US
dc.subjectCell biologyen_US
dc.subjectLSFen_US
dc.subjectHCCen_US
dc.subjectFQIen_US
dc.subjectMitotic arresten_US
dc.subjectApoptosisen_US
dc.subjectTranscription factor LSFen_US
dc.subjectThymidylate synthase expressionen_US
dc.subjectHuman-melanoma cellsen_US
dc.subjectC-MYCen_US
dc.subjectMechanismen_US
dc.subjectOncogeneen_US
dc.subjectProteinen_US
dc.subjectIdentificationen_US
dc.subjectInactivationen_US
dc.subjectActivationen_US
dc.subjectAnimalsen_US
dc.subjectAntineoplastic agentsen_US
dc.subjectBenzodioxolesen_US
dc.subjectCarcinoma, hepatocellularen_US
dc.subjectCell cycle checkpointsen_US
dc.subjectCell line, tumoren_US
dc.subjectCell proliferationen_US
dc.subjectDNA-binding proteinsen_US
dc.subjectDiethylnitrosamineen_US
dc.subjectDose-response relationship, drugen_US
dc.subjectGenes, mycen_US
dc.subjectGenetic predisposition to diseaseen_US
dc.subjectLiver neoplasms, experimentalen_US
dc.subjectMice, transgenicen_US
dc.subjectMitosisen_US
dc.subjectMolecular targeted therapyen_US
dc.subjectNeovascularization, pathologicen_US
dc.subjectPhenotypeen_US
dc.subjectQuinolonesen_US
dc.subjectSignal transductionen_US
dc.subjectTime factorsen_US
dc.subjectTranscription factorsen_US
dc.subjectCell line, tumoren_US
dc.subjectMice, transgenicen_US
dc.subjectHumansen_US
dc.subjectCarcinoma, hepatocellularen_US
dc.subjectLiver neoplasms, experimentalen_US
dc.subjectNeovascularization, pathologicen_US
dc.subjectDiethylnitrosamineen_US
dc.subjectQuinolonesen_US
dc.subjectDNA-binding proteinsen_US
dc.subjectCell cycle checkpointsen_US
dc.subjectmitotic arresten_US
dc.subjectOncology and carcinogenesisen_US
dc.titleSmall molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): evaluation using an endogenous HCC modelen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.18632/oncotarget.4656
pubs.elements-sourceweb-of-scienceen_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Arts & Sciencesen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Biologyen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Chemistryen_US
pubs.publication-statusPublisheden_US
dc.identifier.mycv41921


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