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dc.contributor.authorNalli, Ancy D.en_US
dc.contributor.authorBrown, Lauren E.en_US
dc.contributor.authorThomas, Cheryl L.en_US
dc.contributor.authorSayers, Thomas J.en_US
dc.contributor.authorPorco, John A.en_US
dc.contributor.authorHenrich, Curtis J.en_US
dc.date.accessioned2019-02-05T14:29:15Z
dc.date.available2019-02-05T14:29:15Z
dc.date.issued2018-11-30
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000451748700041&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e74115fe3da270499c3d65c9b17d654
dc.identifier.citationAncy D. Nalli, Lauren E. Brown, Cheryl L. Thomas, Thomas J. Sayers, John A. Porco, Curtis J. Henrich. 2018. "Sensitization of renal carcinoma cells to TRAIL-induced apoptosis by rocaglamide and analogs." SCIENTIFIC REPORTS, Volume 8, pp. ? - ? (11). https://doi.org/10.1038/s41598-018-35908-0
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/2144/33279
dc.description.abstractRocaglamide has been reported to sensitize several cell types to TRAIL-induced apoptosis. In recent years, advances in synthetic techniques have led to generation of novel rocaglamide analogs. However, these have not been extensively analyzed as TRAIL sensitizers, particularly in TRAIL-resistant renal cell carcinoma cells. Evaluation of rocaglamide and analogs identified 29 compounds that are able to sensitize TRAIL-resistant ACHN cells to TRAIL-induced, caspase-dependent apoptosis with sub-µM potency which correlated with their potency as protein synthesis inhibitors and with loss of cFLIP protein in the same cells. Rocaglamide alone induced cell cycle arrest, but not apoptosis. Rocaglates averaged 4–5-fold higher potency as TRAIL sensitizers than as protein synthesis inhibitors suggesting a potential window for maximizing TRAIL sensitization while minimizing effects of general protein synthesis inhibition. A wide range of other rocaglate effects (e.g. on JNK or RAF-MEK-ERK signaling, death receptor levels, ROS, ER stress, eIF4E phosphorylation) were assessed, but did not contribute to TRAIL sensitization. Other than a rapid loss of MCL-1, rocaglates had minimal effects on mitochondrial apoptotic pathway proteins. The identification of structurally diverse/mechanistically similar TRAIL sensitizing rocaglates provides insights into both rocaglate structure and function and potential further development for use in RCC-directed combination therapy.en_US
dc.description.sponsorshipThis project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported [in part] by the Intramural Research Program of NIH, Frederick. National Lab, Center for Cancer Research. Research performed at Boston University was supported in part by NIH R35 GM118173. Work at the BU-CMD is supported by R24 GM111625. (HHSN261200800001E - National Cancer Institute, National Institutes of Health; Intramural Research Program of NIH, Frederick. National Lab, Center for Cancer Research; R35 GM118173 - NIH; R24 GM111625)en_US
dc.format.extent11 p.en_US
dc.languageEnglish
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofScientific Reports
dc.rightsAttribution 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectScience & technologyen_US
dc.subjectMultidisciplinary sciencesen_US
dc.subjectUbiquitin ligase itchen_US
dc.subjectCancer-cellsen_US
dc.subjectC-flipen_US
dc.subjectResistanceen_US
dc.subjectInhibitionen_US
dc.subjectActivationen_US
dc.subjectDerivativesen_US
dc.subjectDeathen_US
dc.subjectChemotherapyen_US
dc.subjectFlavaglinesen_US
dc.titleSensitization of renal carcinoma cells to TRAIL-induced apoptosis by rocaglamide and analogsen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.1038/s41598-018-35908-0
pubs.elements-sourcemanual-entryen_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 Chemistryen_US
pubs.publication-statusPublisheden_US


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International