Source:http://linkedlifedata.com/resource/pubmed/id/14633716
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
22
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| pubmed:dateCreated |
2003-11-24
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| pubmed:abstractText |
The effects of geldanamycin (GA), 17-(3-aminopropylamino)-17-demethoxygeldanamycin (AP-GA), and N-(2-hydroxypropyl)methacrylamide copolymer-AP-GA conjugate [P(AP-GA)] on A2780 human ovarian carcinoma cells at an equitoxic dose (2x IC(50)) were compared by the gene expression array analysis. All treatments resulted in similar gene expression profiles up to 12 h (e.g., down-regulation of CDK4 and up-regulation of APAF-1), although P(AP-GA)-treated cells showed delayed gene expression because of time-dependent internalization of the conjugate and intracellular drug release from P(AP-GA). However, AP-GA-treated cells showed elevated expression of HSP70 and HSP27 after 6 h compared with that observed by GA and P(AP-GA) treatments. Depletion of C-Raf, an HSP90 client protein, was observed in all treatments up to 12 h. Confocal microscopy using mesochlorin e(6) as a model drug revealed that drug release caused by the lysosomal cleavage of glycylphenylalanylleucylglycine oligopeptide spacer, used as GA derivative copolymer attachment/release point, was moderately fast. These results suggested that AP-GA treatment may activate stress-response pathways, whereas P(AP-GA) treatment may suppress them and trigger signaling pathways essential to cell growth arrest and death by inducing an HSP90-active factor. Although GA and P(AP-GA) treatments induced a time-dependent increase in HSP70 and HSP27 protein expression (detected by Western blotting analysis), AP-GA treatment resulted in more rapid and more intense expression of both proteins. Our results suggest that conjugation of AP-GA to N-(2-hydroxypropyl)methacrylamide copolymer may be able to modulate the cell stress responses induced by AP-GA because of differences in its internalization mechanism, subcellular localization, and intracellular concentration gradients.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Duxon,
http://linkedlifedata.com/resource/pubmed/chemical/HSP27 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HSP70 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HSPB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Polymethacrylic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Quinones,
http://linkedlifedata.com/resource/pubmed/chemical/geldanamycin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0008-5472
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
63
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
7876-82
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:14633716-Antibiotics, Antineoplastic,
pubmed-meshheading:14633716-Benzoquinones,
pubmed-meshheading:14633716-Blotting, Western,
pubmed-meshheading:14633716-Cell Line, Tumor,
pubmed-meshheading:14633716-Female,
pubmed-meshheading:14633716-Gene Expression Profiling,
pubmed-meshheading:14633716-HSP27 Heat-Shock Proteins,
pubmed-meshheading:14633716-HSP70 Heat-Shock Proteins,
pubmed-meshheading:14633716-Heat-Shock Proteins,
pubmed-meshheading:14633716-Humans,
pubmed-meshheading:14633716-Inhibitory Concentration 50,
pubmed-meshheading:14633716-Lactams, Macrocyclic,
pubmed-meshheading:14633716-Microscopy, Fluorescence,
pubmed-meshheading:14633716-Neoplasm Proteins,
pubmed-meshheading:14633716-Ovarian Neoplasms,
pubmed-meshheading:14633716-Polymethacrylic Acids,
pubmed-meshheading:14633716-Quinones,
pubmed-meshheading:14633716-Reverse Transcriptase Polymerase Chain Reaction
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| pubmed:year |
2003
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| pubmed:articleTitle |
Free and N-(2-hydroxypropyl)methacrylamide copolymer-bound geldanamycin derivative induce different stress responses in A2780 human ovarian carcinoma cells.
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| pubmed:affiliation |
Department of Pharmaceutics and Pharmaceutical Chemistry/Center for Controlled Chemical Delivery (CCCD), University of Utah, 30 South 2000 East, Room 301, Salt Lake City, UT 84112, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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