Document Detail

Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of non-small cell lung cancer cells.
MedLine Citation:
PMID:  19628293     Owner:  NLM     Status:  MEDLINE    
The effects of dithiolethione modified valproate, diclofenac and sulindac on non-small cell lung cancer (NSCLC) cells were investigated. Sulfur(S)-valproate and S-diclofenac at 1 microg/ml concentrations significantly reduced prostaglandin (PG)E(2) levels in NSCLC cell lines A549 and NCI-H1299 as did the COX-2 inhibitor DuP-697. In vitro, S-valproate, S-diclofenac and S-sulindac half-maximally inhibited the clonal growth of NCI-H1299 cells at 6, 6 and 15 microg/ml, respectively. Using the MTT assay, 10 microg/ml S-valproate, NO-aspirin and Cay10404, a selective COX-2 inhibitor, but not SC-560, a selective COX-1 inhibitor, inhibited the growth of A549 cells. In vivo, 18mg/kg i.p. of S-valproate and S-diclofenac, but not S-sulindac, significantly inhibited A549 or NCI-H1299 xenograft proliferation in nude mice, but had no effect on the nude mouse body weight. The mechanism by which S-valproate and S-diclofenac inhibited the growth of NSCLC cells was investigated. Nitric oxide-aspirin but not S-valproate caused apoptosis of NSCLC cells. By Western blot, S-valproate and S-diclofenac increased E-cadherin but reduced vimentin and ZEB1 (a transcriptional suppressor of E-cadherin) protein expression in NSCLC cells. Because S-valproate and S-diclofenac inhibit the growth of NSCLC cells and reduce PGE(2) levels, they may prove beneficial in the chemoprevention and/or therapy of NSCLC.
Terry W Moody; Christopher Switzer; Wilmarie Santana-Flores; Lisa A Ridnour; Marc Berna; Michelle Thill; Robert T Jensen; Anna Sparatore; Piero Del Soldato; Grace C Yeh; David D Roberts; Giuseppe Giaccone; David A Wink
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2009-07-23
Journal Detail:
Title:  Lung cancer (Amsterdam, Netherlands)     Volume:  68     ISSN:  1872-8332     ISO Abbreviation:  Lung Cancer     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-03-29     Completed Date:  2010-09-07     Revised Date:  2013-12-25    
Medline Journal Info:
Nlm Unique ID:  8800805     Medline TA:  Lung Cancer     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  154-60     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Ireland Ltd.
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MeSH Terms
Anethole Trithione / metabolism
Cadherins / biosynthesis*,  genetics
Carcinoma, Non-Small-Cell Lung / drug therapy*,  genetics,  metabolism,  pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclooxygenase Inhibitors / pharmacology
Diclofenac / chemistry,  pharmacology*
Dinoprostone / biosynthesis,  genetics
Gene Expression Regulation, Neoplastic / drug effects
Isoxazoles / pharmacology
Lung Neoplasms / drug therapy*,  genetics,  metabolism,  pathology
Mice, Nude
Neoplasm Transplantation
Pyrazoles / pharmacology
Sulfones / pharmacology
Valproic Acid / chemistry,  pharmacology*
Grant Support
Reg. No./Substance:
0/3-(4-methylsulfonylphenyl)-4-phenyl-5-trifluoromethylisoxazole; 0/Cadherins; 0/Cyclooxygenase Inhibitors; 0/Isoxazoles; 0/Pyrazoles; 0/SC 560; 0/Sulfones; 144O8QL0L1/Diclofenac; 614OI1Z5WI/Valproic Acid; K7Q1JQR04M/Dinoprostone; QUY32964DJ/Anethole Trithione

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