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dc.contributor.authorZhu, Lijiaen_US
dc.contributor.authorQi, Jien_US
dc.contributor.authorChiao, Christine Ya-Chien_US
dc.contributor.authorZhang, Qiangen_US
dc.contributor.authorPorco, John A.en_US
dc.contributor.authorFaller, Douglas V.en_US
dc.contributor.authorDai, Yanen_US
dc.coverage.spatialGreeceen_US
dc.date2014-07-10
dc.date.accessioned2018-01-25T17:32:38Z
dc.date.available2018-01-25T17:32:38Z
dc.date.issued2014-11
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/25189993
dc.identifier.citationZhu, l., Qi, J., Chiao, C.Y., Zhang, Q., Porco Jr, J.A., Faller, d.V., & Dai, Y. (2014). Identification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities. International Journal of Oncology, 45, 2128-2136. https://doi.org/10.3892/ijo.2014.2639
dc.identifier.issn1791-2423
dc.identifier.urihttps://hdl.handle.net/2144/26414
dc.description.abstractSIRT1, a class III histone deacetylase, plays a critical role in regulating cancer cell growth, migration and invasion, which makes it a potential target for cancer therapeutics. In this study, we screened derivatives of several groups of natural products and identified a novel SIRT1 inhibitor JQ-101, a synthetic derivative of the polyprenylated acylphloroglucinol (PPAP) natural products, with an IC(50) for SIRT1 of 30 µM in vitro, with 5-fold higher activity for SIRT1 vs. SIRT2. Exposure of tumor cells to JQ-101 significantly enhanced acetylation of p53 and histone H4K16 at known sites of SIRT1 deacetylation, validating SIRT1 as its cellular target. JQ-101 suppressed cancer cell growth and survival by targeting SIRT1, and also exhibited selective cytotoxicity towards a panel of human tumor cell lines, while producing no toxicity in two normal human cell types at comparable concentrations. JQ-101 induced both apoptosis and cell senescence, and suppressed cancer cell invasion in vitro. In summary, we have identified JQ-101 as a new SIRT1 inhibitor which may have potential application in cancer treatment through its ability to induce tumor cell apoptosis and senescence and suppress cancer cell invasion.en_US
dc.description.sponsorshipCA164245 - NCI NIH HHS; R01 CA101992 - NCI NIH HHS; R21 CA129046 - NCI NIH HHS; R21 CA141036 - NCI NIH HHS; P50 GM067041 - NIGMS NIH HHS; UL1RR025771 - NCRR NIH HHS; CA101992 - NCI NIH HHS; UL1 RR025771 - NCRR NIH HHS; GM-073855 - NIGMS NIH HHS; CA129046 - NCI NIH HHS; R21 CA164245 - NCI NIH HHS; GM-067041 - NIGMS NIH HHS; CA141036 - NCI NIH HHS; R01 GM073855 - NIGMS NIH HHSen_US
dc.format.extent2128 - 2136en_US
dc.languageeng
dc.relation.ispartofInt J Oncol
dc.subjectLife sciences & biomedicineen_US
dc.subjectOncologyen_US
dc.subjectSIRT1 inhibitoren_US
dc.subjectPolyprenylated acylphloroglucinolen_US
dc.subjectCancer cell growthen_US
dc.subjectCancer cell invasionen_US
dc.subjectSmall-molecule inhibitoren_US
dc.subjectProstate canceren_US
dc.subjectCell migrationen_US
dc.subjectBreast canceren_US
dc.subjectLung metastasisen_US
dc.subjectDown-regulationen_US
dc.subjectPoor prognosisen_US
dc.subjectDU145 cellsen_US
dc.subjectApoptosisen_US
dc.subjectCell movementen_US
dc.subjectCell proliferationen_US
dc.subjectCellular senescenceen_US
dc.subjectGene expression regulation, neoplasticen_US
dc.subjectHumansen_US
dc.subjectNeoplasm invasivenessen_US
dc.subjectNeoplasmsen_US
dc.subjectPhloroglucinolen_US
dc.subjectSirtuin 1en_US
dc.subjectSirtuin 2en_US
dc.subjectCell agingen_US
dc.subjectPolyprenylated acylphloroglucinolen_US
dc.subjectCancer cell growthen_US
dc.subjectCancer cell invasionen_US
dc.subjectOncology and carcinogenesisen_US
dc.titleIdentification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities.en_US
dc.typeArticleen_US
dc.identifier.doi10.3892/ijo.2014.2639
dc.identifier.pmid25189993
pubs.elements-sourcepubmeden_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.organisational-groupBoston University, School of Medicineen_US
pubs.publication-statusPublisheden_US


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