Source:http://linkedlifedata.com/resource/pubmed/id/14556662
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2003-10-14
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pubmed:abstractText |
Since ethacrynic acid (EA), an SH modifier as well as glutathione S-transferase (GST) inhibitor, has been suggested to induce apoptosis in some cell lines, its effects on a human colon cancer cell line DLD-1 were examined. EA enhanced cell proliferation at 20-40 microM, while it caused cell death at 60-100 microM. Caspase inhibitors did not block cell death and DNA ladder formation was not detected. Poly(ADP-ribose) polymerase, however, was cleaved into an 82-kDa fragment, different from an 85-kDa fragment that is specific for apoptosisis. The 82-kDa fragment was not recognized by antibody against PARP fragment cleaved by caspase 3. N-Acetyl-L-cysteine (NAC) completely inhibited EA-induced cell death, but 3(2)-t-butyl-4-hydroxyanisole or pyrrolidinedithiocarbamate ammonium salt did not. Glutathione (GSH) levels were dose-dependently increased in cells treated with EA and this increase was hardly affected by NAC addition. Mitogen-activated protein kinase (MAPK) kinase (MEK) 1, extracellular signal-regulated kinase (ERK) 1 and GST P1-1 were increased in cells treated with 25-75 microM EA, while c-Jun N-terminal kinase (JNK) 1 and p38 MAPK were markedly decreased by 100 microM EA. NAC repressed EA-induced alterations in these MAPKs and GST P1-1. p38 MAPK inhibitors, SB203580 and FR167653, dose-dependently enhanced EA-induced cell death. An MEK inhibitor, U0126, did not affect EA-induced cell death. These studies revealed that EA induced cell death concomitantly with a novel PARP fragmentation, but without DNA fragmentation. p38 MAPK was suggested to play an inhibitory role in EA-induced cell death.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ethacrynic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/GSTP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione S-Transferase pi,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1347-9032
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
94
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
886-93
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14556662-Acetylcysteine,
pubmed-meshheading:14556662-Antioxidants,
pubmed-meshheading:14556662-Cell Death,
pubmed-meshheading:14556662-Cell Division,
pubmed-meshheading:14556662-Cell Line, Tumor,
pubmed-meshheading:14556662-Colonic Neoplasms,
pubmed-meshheading:14556662-Enzyme Inhibitors,
pubmed-meshheading:14556662-Ethacrynic Acid,
pubmed-meshheading:14556662-Fluorescence,
pubmed-meshheading:14556662-Glutathione,
pubmed-meshheading:14556662-Glutathione S-Transferase pi,
pubmed-meshheading:14556662-Glutathione Transferase,
pubmed-meshheading:14556662-Humans,
pubmed-meshheading:14556662-Isoenzymes,
pubmed-meshheading:14556662-Mitogen-Activated Protein Kinases
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pubmed:year |
2003
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pubmed:articleTitle |
Characterization of cell death induced by ethacrynic acid in a human colon cancer cell line DLD-1 and suppression by N-acetyl-L-cysteine.
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pubmed:affiliation |
Second Department of Biochemistry, Hirosaki University School of Medicine, Hirosaki, Aomori 036-8562, Japan. tsuchida@cc.hirosaki-u.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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