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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2002-1-29
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pubmed:abstractText |
We have examined the effects of 12 glucocorticoids as inhibitors of A549 cell growth. Other than cortisone and prednisone, all the glucocorticoids inhibited cell growth and this was strongly correlated (r=0.91) with inhibition of prostaglandin (PG)E(2) formation. The molecular mechanism by which the active steroids prevented PGE(2) synthesis was examined and three groups were identified. Group A drugs did not inhibit arachidonic acid release but inhibited the induction of COX2. Group B drugs were not able to inhibit the induction of COX2 but inhibited arachidonic acid release through suppression of cPLA(2) activation. Group C drugs were apparently able to bring about both effects. The inhibitory actions of all steroids was dependent upon glucocorticoid receptor occupation since RU486 reversed their effects. However, group A acted through the NF-kappaB pathway to inhibit COX2 as the response was blocked by the inhibitor geldanamycin which prevents dissociation of GR and the effect was blocked by APDC, the NF-kappaB inhibitor. On the other hand, the group B drugs were not inhibited by NF-kappaB inhibitors or geldanamycin but their effect was abolished by the src inhibitor PP2. Group C drugs depended on both pathways. In terms of PGE(2) generation, there is clear evidence of two entirely separate mechanisms of glucocorticoid action, one of which correlates with NF-kappaB mediated genomic actions whilst the other, depends upon rapid effects on a cell signalling system which does not require dissociation of GR. The implications for these findings are discussed.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-10193529,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-10586893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-10656875,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-10659992,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-10807665,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-10991918,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-11005817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-11090106,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-11258691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-1883691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-2243084,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-2853748,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-3038508,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-7646551,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-7985093,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-8048967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-8072494,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-8076604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-8521509,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-8651621,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-8694860,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-8733570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-889307,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-9178099,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-9291100,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-9338790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-9407028,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-9520807,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-9535028,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-9563368,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-9571182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-9588727,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-9604929,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-9891987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11815387-98977
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0007-1188
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
135
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
511-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:11815387-Arachidonic Acid,
pubmed-meshheading:11815387-Cell Division,
pubmed-meshheading:11815387-Cyclooxygenase 2,
pubmed-meshheading:11815387-Dexamethasone,
pubmed-meshheading:11815387-Dinoprostone,
pubmed-meshheading:11815387-Enzyme Activation,
pubmed-meshheading:11815387-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:11815387-Glucocorticoids,
pubmed-meshheading:11815387-Humans,
pubmed-meshheading:11815387-Isoenzymes,
pubmed-meshheading:11815387-Membrane Proteins,
pubmed-meshheading:11815387-Phospholipases A,
pubmed-meshheading:11815387-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:11815387-Signal Transduction,
pubmed-meshheading:11815387-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
Different glucocorticoids vary in their genomic and non-genomic mechanism of action in A549 cells.
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pubmed:affiliation |
Department of Biochemical Pharmacology, The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine & Dentistry (Queen Mary and Westfield College), Charterhouse Square, London EC1M 6BQ. J.Croxtall@qmul.ac.uk
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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