Please use this identifier to cite or link to this item:
Title: Curcumin sensitizes acute promyelocytic leukemia cells to unfolded protein response-induced apoptosis by blocking the loss of misfolded N-CoR protein
Authors: Ng, A.P.P.
Chng, W.J.
Khan, M. 
Issue Date: Jul-2011
Citation: Ng, A.P.P., Chng, W.J., Khan, M. (2011-07). Curcumin sensitizes acute promyelocytic leukemia cells to unfolded protein response-induced apoptosis by blocking the loss of misfolded N-CoR protein. Molecular Cancer Research 9 (7) : 878-888. ScholarBank@NUS Repository.
Abstract: Acute promyelocytic leukemia (APL) is characterized by accumulation of apoptosis-resistant immature promyelocytic cells in the bone marrow and peripheral blood. We have shown that endoplasmic reticulum (ER)-associated degradation (ERAD) and protease-mediated degradation of misfolded nuclear receptor corepressor (N-CoR) confer resistance to unfolded protein response (UPR)-induced apoptosis in APL. These findings suggest that therapeutic inhibition of N-CoR misfolding or degradation may promote growth arrest in APL cells by sensitizing them to UPR-induced apoptosis. On the basis of this hypothesis, we tested the effects of several known protein conformation- modifying agents on the growth and survival of APL cells and identified curcumin, a natural component of turmeric, as a potent growth inhibitor of APL cells. Curcumin selectively inhibited the growth and promoted apoptosis in both primary and secondary leukemic cells derived from APL. The curcumin-nduced apoptosis of APL cells was triggered by an amplification of ER stress, possibly from the accumulation of misfolded N-CoR protein in the ER. Curcumin promoted this net accumulation of aberrantly phosphorylated misfolded N-CoR protein by blocking its ERAD and protease-mediated degradation, which then led to the activation of UPR-induced apoptosis in APL cells. The activation of UPR by curcumin was manifested by phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and eukaryotic translation initiation factor 2 alpha (eIF2α), and upregulation of C/EBP homologous protein (CHOP) and GADD34, the principal mediators of proapoptotic UPR. These findings identify the therapeutic potential of curcumin in APL and further establish the rationale of misfolded N-CoR protein as an attractive molecular target in APL. ©2011 AACR.
Source Title: Molecular Cancer Research
ISSN: 15417786
DOI: 10.1158/1541-7786.MCR-10-0545
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on May 29, 2023


checked on May 29, 2023

Page view(s)

checked on May 25, 2023

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.