Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/33291
Title: Inhibition of misfolded N-CoR induced survival pathway in APL by Artemisinin
Authors: YEO HUI LING, ANGIE
Keywords: Acute promyelocytic leukemia, N-CoR, misfolding, autophagy, artemisinin
Issue Date: 9-Dec-2011
Source: YEO HUI LING, ANGIE (2011-12-09). Inhibition of misfolded N-CoR induced survival pathway in APL by Artemisinin. ScholarBank@NUS Repository.
Abstract: Acute promyelocytic leukemia (APL) is characterized by PML-RARa, a fusion protein resulting from a chromosomal translocation between the promyelocytic leukemia (PML) gene and retinoic acid receptor a (RARa) gene. PML-RARa was shown to promote misfolding and accumulation of nuclear receptor co-repressor (N-CoR) in the endoplasmic reticulum (ER) and cause unfolded protein response (UPR)-linked apoptosis. However in APL cells, N-CoR was found to be degraded, relieving ER stress and escaping cell death. Previous results also showed that autophagy was elevated in APL cells and drug inhibition of autophagy led to a stabilization of N-CoR with corresponding decrease in adenosine triphosphate (ATP) levels, suggesting a possible function of N-CoR where APL cells may use its degradation through autophagy to provide an alternative energy source for cancer cell survival. Here, I report a drug artemisinin as a potential therapeutic agent which selectively promotes growth inhibition and apoptosis in APL cells. Artemisinin enhanced the degradation of N-CoR, which could be restabilized by treatment with a proteasome inhibitor. Levels of autophagic and survival markers, and ATP in APL cells also decreased after artemisinin treatment. These findings suggest that artemisinin possibly enhances the proteasomal degradation of misfolded N-CoR, thus depriving cancer cells of the extra energy source generated by the autophagic degradation of misfolded proteins.
URI: http://scholarbank.nus.edu.sg/handle/10635/33291
Appears in Collections:Master's Theses (Open)

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