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dc.contributor.authorTheodoropoulou, Sofia
dc.contributor.authorBrodowska, Katarzyna
dc.contributor.authorKayama, Maki
dc.contributor.authorMorizane, Yuki
dc.contributor.authorMiller, Joan Whitten
dc.contributor.authorGragoudas, Evangelos Stelios
dc.contributor.authorVavvas, Demetrios
dc.date.accessioned2013-05-09T13:27:44Z
dc.date.issued2013
dc.identifier.citationTheodoropoulou, Sofia, Katarzyna Brodowska, Maki Kayama, Yuki Morizane, Joan Whitten Miller, Evangelos Stelios Gragoudas, and Demetrios Vavvas. 2013. Aminoimidazole carboxamide ribonucleotide (AICAR) inhibits the growth of retinoblastoma in vivo by decreasing angiogenesis and inducing apoptosis. PLoS ONE 8(1): e52852.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10612916
dc.description.abstract5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), an analog of AMP is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. Recently, we showed that AICAR-induced AMPK activation inhibits the growth of retinoblastoma cells in vitro by decreasing cyclins and by inducing apoptosis and S-phase arrest. In this study, we investigated the effects of AMPK activator AICAR on the growth of retinoblastoma in vivo. Intraperitoneal injection of AICAR resulted in 48% growth inhibition of Y79 retinoblastoma cell tumors in mice. Tumors isolated from mice treated with AICAR had decreased expression of Ki67 and increased apoptotic cells (TUNEL positive) compared with the control. In addition, AICAR treatment suppressed significantly tumor vessel density and macrophage infiltration. We also showed that AICAR administration resulted in AMPK activation and mTOR pathway inhibition. Paradoxically observed down-regulation of p21, which indicates that p21 may have a novel function of an oncogene in retinoblastoma tumor. Our results indicate that AICAR treatment inhibited the growth of retinoblastoma tumor in vivo via AMPK/mTORC1 pathway and by apoptogenic, anti-proliferative, anti-angiogenesis mechanism. AICAR is a promising novel non-chemotherapeutic drug that may be effective as an adjuvant in treating Retinoblastoma.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0052852en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536763/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectBiochemistryen_US
dc.subjectDrug Discoveryen_US
dc.subjectSmall Moleculesen_US
dc.subjectBiotechnologyen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectSignal Transductionen_US
dc.subjectSignaling Cascadesen_US
dc.subjectApoptotic Signaling Cascadeen_US
dc.subjectSignaling in Cellular Processesen_US
dc.subjectApoptotic Signalingen_US
dc.subjectCell Deathen_US
dc.subjectNeuroscienceen_US
dc.subjectSensory Systemsen_US
dc.subjectVisual Systemen_US
dc.subjectMedicineen_US
dc.subjectDrugs and Devicesen_US
dc.subjectOphthalmologyen_US
dc.subjectOcular Tumorsen_US
dc.subjectDrug Researchen_US
dc.subjectDrug Developmenten_US
dc.titleAminoimidazole Carboxamide Ribonucleotide (AICAR) Inhibits the Growth of Retinoblastoma In Vivo by Decreasing Angiogenesis and Inducing Apoptosisen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorBrodowska, Katarzyna
dc.date.available2013-05-09T13:27:44Z
dc.identifier.doi10.1371/journal.pone.0052852*
dash.contributor.affiliatedGragoudas, Evangelos
dash.contributor.affiliatedBrodowska, Katarzyna
dash.contributor.affiliatedMiller, Joan
dash.contributor.affiliatedVavvas, Demetrios


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