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https://scholarbank.nus.edu.sg/handle/10635/49402
DC Field | Value | |
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dc.title | Antiproliferative activity of curcumin analogs on acute promyelocytic leukemia : Synthesis and mode of action studies | |
dc.contributor.author | TAN KHENG LIN | |
dc.date.accessioned | 2014-02-28T18:01:53Z | |
dc.date.available | 2014-02-28T18:01:53Z | |
dc.date.issued | 2013-08-16 | |
dc.identifier.citation | TAN KHENG LIN (2013-08-16). Antiproliferative activity of curcumin analogs on acute promyelocytic leukemia : Synthesis and mode of action studies. ScholarBank@NUS Repository. | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/49402 | |
dc.description.abstract | Acute promyelocytic leukemia results from the fusion of promyelocytic leukemia and retinoic acid receptor which induces a conformational change in the nuclear receptor co-repressor (N-CoR) protein. 78 curcumin analogs were synthesized and evaluated on APL cell lines (NB4, NB4-R1), non-APL cell lines (HL60, K562) and non-malignant cell lines (IMR90, MCF10A). Structural features contributing to activity and selectivity were assessed. Compounds 11, 22 and 41 were found to induce accumulation of misfolded N-CoR at concentrations significantly lower than curcumin. Curcumin and 41 activate the protein processing in the endoplasmic reticulum pathway resulting in the activation of unfolded protein response (UPR) pathway. These lead compounds inhibited 26S proteasome and activated ER stress-induced apoptosis. In conclusion, these curcuminoids were promising candidates that activate ER stress-induced apoptosis of APL cells via the novel misfolded N-CoR pathway. | |
dc.language.iso | en | |
dc.subject | Acute promyelocytic leukemia, curcumin, nuclear receptor co-repressor, endoplasmic reticulum stress, unfolded protein response, proteasome | |
dc.type | Thesis | |
dc.contributor.department | PHARMACY | |
dc.contributor.supervisor | GO MEI LIN | |
dc.contributor.supervisor | CHIN TAN MIN | |
dc.description.degree | Ph.D | |
dc.description.degreeconferred | DOCTOR OF PHILOSOPHY | |
dc.identifier.isiut | NOT_IN_WOS | |
Appears in Collections: | Ph.D Theses (Open) |
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TanKhengLin_PhD Thesis.pdf | 5.38 MB | Adobe PDF | OPEN | None | View/Download |
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