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Cryptotanshinone induces cell cycle arrest and apoptosis of multidrug resistant human chronic myeloid leukemia cells by inhibiting the activity of eukaryotic initiation factor 4E.
MedLine Citation:
PMID:  22614784     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cryptotanshinone (CPT), a diterpene quinone isolated from Salvia miltiorrhiza, is recently reported to have obvious anticancer activities against diverse cancer cells. However, the effect and regulatory mechanism of CPT remain unclear in human chronic myeloid leukemia (CML) cells. In this study, we investigated the antiproliferative activity of CPT on the multidrug resistant CML cells K562/ADM. Our results demonstrated that CPT decreased the cell viability of K562/ADM cells by inducing cell cycle arrest and apoptosis through suppressing the expression of cyclin D1 and Bcl-2. Further studies indicated that CPT mainly functions at post-transcriptional levels, suggesting the involvement of eukaryotic initiation factor 4E (eIF4E). CPT significantly reduced the expression and activity of eIF4E in K562/ADM cells. Overexpression of eIF4E obvious conferred resistance to the CPT antiproliferation and proapoptotic activity as well as the cyclin D1 and Bcl-2 expressions. Knockdown of eIF4E significantly reduced the inhibitory effect of CPT in K562/ADM, confirming the participation of eIF4E during CPT function process. More importantly, the relative inhibitory efficiency of CPT positively correlated with the reductions on eIF4E in primary CML specimens. These results demonstrated that CPT played antitumor roles in K562/ADM cells by inhibiting the eIF4E regulatory system. Our results provide a novel anticancer mechanism of CPT in human CML cells.
Authors:
Yuqing Ge; Rubin Cheng; Yuhong Zhou; Jianping Shen; Laijun Peng; Xiaofeng Xu; Qun Dai; Pei Liu; Haibing Wang; Xiaoqiong Ma; Jia Jia; Zhe Chen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-22
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  -     ISSN:  1573-4919     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou, 310006, China.
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