Document Detail


Diazoxide-mediated growth inhibition in human lung cancer cells via downregulation of beta-catenin-mediated cyclin D1 transcription.
MedLine Citation:
PMID:  19052819     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Treatment of various types of cells with the mitochondrial ATP-sensitive K(+) channel opener, diazoxide, preconditions cells to subsequent injuries and inhibits apoptosis. However, the role and mechanism(s) of diazoxide in solid tumor cell growth are largely unknown. Here we demonstrate that diazoxide inhibited the proliferation of lung cancer cells as well as the transcription of cell cycle-related protein Cyclin D1. Cyclin D1 overexpression inhibited the negative role of diazoxide in cell cycle progression. We further explored the mechanisms by which diazoxide affected Cyclin D1 transcription and found that the beta-catenin transcription factor was downregulated by diazoxide, with a corresponding decrease in Cyclin D1 promoter activity. Taken together, these results suggest that diazoxide inhibits lung cancer cell proliferation via downregulation of Cyclin D1 transcription, which may have important therapeutic implications in lung cancer patients.
Authors:
Jianyong Ding; Di Ge; Weigang Guo; Chunlai Lu
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Publication Detail:
Type:  Journal Article     Date:  2008-12-04
Journal Detail:
Title:  Lung     Volume:  187     ISSN:  0341-2040     ISO Abbreviation:  Lung     Publication Date:    2009 Jan-Feb
Date Detail:
Created Date:  2009-01-15     Completed Date:  2009-04-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7701875     Medline TA:  Lung     Country:  United States    
Other Details:
Languages:  eng     Pagination:  61-7     Citation Subset:  IM    
Affiliation:
Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Non-Small-Cell Lung / metabolism,  pathology
Cell Line, Tumor
Cell Proliferation / drug effects*
Cyclin D1 / genetics,  metabolism*
Diazoxide / pharmacology*
Down-Regulation / drug effects*
G1 Phase / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Humans
Lung Neoplasms / metabolism*,  pathology*
Plasmids
RNA, Messenger / metabolism
Transfection
beta Catenin / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/beta Catenin; 136601-57-5/Cyclin D1; 364-98-7/Diazoxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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