Document Detail


Cucurbitacin D induces fetal hemoglobin synthesis in K562 cells and human hematopoietic progenitors through activation of p38 pathway and stabilization of the γ-globin mRNA.
MedLine Citation:
PMID:  20926322     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The search for novel therapeutic candidates targeting fetal hemoglobin (HbF) activation to reduce the imbalance of globin genes is regarded as a promising approach for the clinical management of sickle cell disease and β-thalassemia. For the first time, we identified cucurbitacin D (CuD), an oxygenated tetracyclic triterpenoid, as a molecular entity inducing γ-globin gene expression and HbF synthesis in K562 cells and human hematopoietic progenitors from a β-thalassemia patient. CuD demonstrated a higher potency in HbF induction when compared with hydroxyurea, which was revealed by the evidence that CuD results in a higher fetal cell percentage and greater HbF content in K562 cells, in addition, to being less cytotoxic. Moreover, CuD also promotes higher HbF expression in primary erythroid cells. In the study to elucidate the molecular mechanisms of CuD's action, our data indicated that CuD-stimulated HbF synthesis was mediated by p38 pathway activation. At the post-transcriptional level, CuD treatment led to a significant elongation of the γ-globin mRNA half-life in K562 cells. Taken together, the results suggest that CuD may be a potential therapeutic agent for β-hemoglobinopathies, including sickle cell anemia and β-thalassemia.
Authors:
Kan Liu; Hongtao Xing; Siwei Zhang; Shuk ming Liu; Ming chiu Fung
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-06
Journal Detail:
Title:  Blood cells, molecules & diseases     Volume:  45     ISSN:  1096-0961     ISO Abbreviation:  Blood Cells Mol. Dis.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9509932     Medline TA:  Blood Cells Mol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  269-75     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Biology, the Chinese University of Hong Kong, Shatin, Hong Kong.
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