Please use this identifier to cite or link to this item: https://doi.org/10.1002/cmdc.201200293
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dc.titleCurcumin Analogues with Potent and Selective Anti-proliferative Activity on Acute Promyelocytic Leukemia: Involvement of Accumulated Misfolded Nuclear Receptor Co-repressor (N-CoR) Protein as a Basis for Selective Activity
dc.contributor.authorTan, K.-L.
dc.contributor.authorKoh, S.-B.
dc.contributor.authorEe, R.P.-L.
dc.contributor.authorKhan, M.
dc.contributor.authorGo, M.-L.
dc.date.accessioned2014-11-26T09:59:33Z
dc.date.available2014-11-26T09:59:33Z
dc.date.issued2012-09
dc.identifier.citationTan, K.-L., Koh, S.-B., Ee, R.P.-L., Khan, M., Go, M.-L. (2012-09). Curcumin Analogues with Potent and Selective Anti-proliferative Activity on Acute Promyelocytic Leukemia: Involvement of Accumulated Misfolded Nuclear Receptor Co-repressor (N-CoR) Protein as a Basis for Selective Activity. ChemMedChem 7 (9) : 1567-1579. ScholarBank@NUS Repository. https://doi.org/10.1002/cmdc.201200293
dc.identifier.issn18607179
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/110729
dc.description.abstractCurcumin arrests the proliferation of acute promyelocytic leukemia (APL) cells by stabilizing the misfolded nuclear receptor co-repressor (N-CoR) protein, thereby sensitizing APL cells to apoptosis induced by the unfolded protein response. This phenomenon was attributed to inhibition of the proteasomal and protease-induced breakdown of misfolded N-CoR by curcumin. Curcumin is, however, a modest inhibitor and affected the viability of APL cells at micromolar concentrations. Modifying curcumin at its conjugated β-diketone linker and terminal phenyl rings yielded potent congeners with sub-micromolar growth inhibitory activities which selectively kill APL cells over non-APL leukemic and nonmalignant cells. Analogues with pronounced APL-selective anti-proliferative activities, as observed in representative dibenzylidenecyclohexanones and dibenzylidenecyclopentanones, strongly promoted the accumulation of misfolded and nonfunctional N-CoR at significantly lower concentrations than their growth inhibitory IC50 values. These compounds also inhibited the human 20S proteasome in an enzyme-based assay, thus providing convincing support for the prevailing hypothesis that impeding the degradation of N-CoR is a key mechanistic event contributing to APL cell death. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1002/cmdc.201200293
dc.sourceScopus
dc.subjectAPL
dc.subjectCurcumin
dc.subjectInhibitors
dc.subjectLeukemia
dc.subjectN-CoR
dc.subjectProtein folding
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentPHARMACY
dc.description.doi10.1002/cmdc.201200293
dc.description.sourcetitleChemMedChem
dc.description.volume7
dc.description.issue9
dc.description.page1567-1579
dc.description.codenCHEMG
dc.identifier.isiut000308042000006
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