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Anti-Cancer Effect of Tectochrysin in NSCLC Cells through Overexpression of Death Receptor and Inactivation of STAT3.
MedLine Citation:
PMID:  25083589     Owner:  NLM     Status:  Publisher    
Phenolic compounds (flavonoids and phenolic acid derivatives) are the most important pharmacologically active ingredients, and these compounds could inhibit proliferation of human cancer cells by inducing of apoptotic cell death. Here we focused on the anticancer effects of tectochrysin on human non-small-cell lung cancer (NSCLC) cells and its mechanism of action. We analysed the activity of tectochrysin on NSCLC cells (A549 and NCI-H460) by use of Western blot analysis for major apoptotic proteins and death receptor expression. We also used EMSA for effects on STAT3 DNA binding activity. Tectochrysin (0-80 μM) suppressed the growth of A549 and NCI-H460 lung cancer cells by inducing of apoptotic cell death in a concentraion dependent manner. Expression of DR3 and Fas as well as DR downstream pro-apoptotic proteins including cleaved caspase-3, cleaved caspase-8, cleaved caspase-9 and Bax were concomitantly increased, but the expression of anti-apoptotic proteins; Bcl-2 was decreased in both cancer cells. In addition, tectochrysin treatment also inhibited phosphorylation of STAT3 in A549 and NCI-H460 cells. However, deletion of DR3 and Fas by small interfering RNA significantly reversed tectochrysin-induced cell growth inhibitory effect as well as down regulation of STAT3 in A549 and NCI-H460 lung cancer cells. Pull down assay and docking model showed interaction of tectochrysin with STAT3. We propose that tectochrysin leads to apoptotic cell death in NSCLC cells through activation of DR3 and Fas expression via inhibition of STAT3 phosphphorylation.
Saet-Byul Oh; Chul Ju Hwang; Suk-Young Song; Yu Yeon Jung; Hyung-Mun Yun; Chang Hyun Sok; Ha Chang Sung; Jin-Mu Yi; Dong Hyun Park; Young Wan Ham; Sang Bae Han; Bang Yeon Hwang; Jin Tae Hong
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-29
Journal Detail:
Title:  Cancer letters     Volume:  -     ISSN:  1872-7980     ISO Abbreviation:  Cancer Lett.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-8-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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