Document Detail


Delta-tocotrienol suppresses Notch-1 pathway by upregulating miR-34a in nonsmall cell lung cancer cells.
MedLine Citation:
PMID:  22438124     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MicroRNAs (miRNAs) are small noncoding RNAs that play critical roles in regulating various cellular functions by transcriptional silencing. miRNAs can function as either oncogenes or tumor suppressors (oncomirs), depending on cancer types. In our study, using miRNA microarray, we observed that downregulation of the Notch-1 pathway, by delta-tocotrienol, correlated with upregulation of miR-34a, in nonsmall cell lung cancer cells (NSCLC). Moreover, re-expression of miR-34a by transfection in NSCLC cells resulted in inhibition of cell growth and invasiveness, induction of apoptosis and enhanced p53 activity. Furthermore, cellular mechanism studies revealed that induction of miR-34a decreased the expression of Notch-1 and its downstream targets including Hes-1, Cyclin D1, Survivin and Bcl-2. Our findings suggest that delta-tocotrienol is a nontoxic activator of mir-34a which can inhibit NSCLC cell proliferation, induce apoptosis and inhibit invasion, and thus offering a potential starting point for the design of novel anticancer agents.
Authors:
Xiangming Ji; Zhiwei Wang; Andreea Geamanu; Arvind Goja; Fazlul H Sarkar; Smiti V Gupta
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-26
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  131     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-09-26     Completed Date:  2013-03-08     Revised Date:  2014-10-19    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2668-77     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 UICC.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects,  genetics
Basic Helix-Loop-Helix Transcription Factors / genetics
Carcinoma, Non-Small-Cell Lung / drug therapy*,  genetics,  metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin D1 / genetics
Down-Regulation / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Homeodomain Proteins / genetics
Humans
Inhibitor of Apoptosis Proteins / genetics
Lung Neoplasms / drug therapy*,  genetics,  metabolism
MicroRNAs / biosynthesis,  genetics*
Neoplasm Invasiveness
Proto-Oncogene Proteins c-bcl-2 / genetics
Receptor, Notch1 / genetics,  metabolism*
Signal Transduction / drug effects*
Transfection / methods
Tumor Suppressor Protein p53 / genetics
Up-Regulation / drug effects
Vitamin E / analogs & derivatives*,  pharmacology
Grant Support
ID/Acronym/Agency:
P30 CA022453/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/BIRC5 protein, human; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Homeodomain Proteins; 0/Inhibitor of Apoptosis Proteins; 0/MIRN34 microRNA, human; 0/MicroRNAs; 0/NOTCH1 protein, human; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptor, Notch1; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 136601-57-5/Cyclin D1; 1406-18-4/Vitamin E; 149348-15-2/HES1 protein, human; 1SRB74OWSI/tocotrienol, delta
Comments/Corrections

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


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