Please use this identifier to cite or link to this item:
https://doi.org/10.1002/cmdc.201200293
DC Field | Value | |
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dc.title | 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 | |
dc.contributor.author | Tan, K.-L. | |
dc.contributor.author | Koh, S.-B. | |
dc.contributor.author | Ee, R.P.-L. | |
dc.contributor.author | Khan, M. | |
dc.contributor.author | Go, M.-L. | |
dc.date.accessioned | 2014-11-26T09:59:33Z | |
dc.date.available | 2014-11-26T09:59:33Z | |
dc.date.issued | 2012-09 | |
dc.identifier.citation | Tan, 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.issn | 18607179 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/110729 | |
dc.description.abstract | Curcumin 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.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1002/cmdc.201200293 | |
dc.source | Scopus | |
dc.subject | APL | |
dc.subject | Curcumin | |
dc.subject | Inhibitors | |
dc.subject | Leukemia | |
dc.subject | N-CoR | |
dc.subject | Protein folding | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | PHARMACY | |
dc.description.doi | 10.1002/cmdc.201200293 | |
dc.description.sourcetitle | ChemMedChem | |
dc.description.volume | 7 | |
dc.description.issue | 9 | |
dc.description.page | 1567-1579 | |
dc.description.coden | CHEMG | |
dc.identifier.isiut | 000308042000006 | |
Appears in Collections: | Staff Publications |
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