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rdf:type |
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lifeskim:mentions |
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0026764,
umls-concept:C0059865,
umls-concept:C0105770,
umls-concept:C0205263,
umls-concept:C0205314,
umls-concept:C0243071,
umls-concept:C0332281,
umls-concept:C0596402,
umls-concept:C0679622,
umls-concept:C0699040,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1871955,
umls-concept:C1871956
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pubmed:issue |
3
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pubmed:dateCreated |
2007-2-21
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pubmed:abstractText |
We have reported previously that R-enantiomer of etodolac (R-etodolac), which is under investigation in phase 2 clinical trials in chronic lymphocytic leukemia, induces potent cytotoxicity at clinically relevant concentrations in multiple myeloma (MM) cells. In this study, we demonstrated that SDX-308 (CEP-18082), a novel analog of etodolac, has more potent cytotoxicity than R-etodolac against both MM cell lines and patient MM cells, including tumor cells resistant to conventional (dexamethasone, doxorubicine, melphalan) and novel (bortezomib) therapies. SDX-308-induced cytotoxicity is triggered by caspase-8/9/3 activation and poly (ADP-ribose) polymerase cleavage, followed by apoptosis. SDX-308 significantly inhibits beta-catenin/T-cell factor pathway by inhibiting nuclear translocation of beta-catenin, thereby downregulating transcription and expression of downstream target proteins including myc and survivin. Neither interleukin-6 nor insulin-like growth factor-1 protect against growth inhibition triggered by SDX-308. Importantly, growth of MM cells adherent to bone marrow (BM) stromal cells is also significantly inhibited by SDX-308. Our data therefore indicate that the novel etodolac analog SDX-308 can target MM cells in the BM milieu.
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pubmed:grant |
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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/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Etodolac,
http://linkedlifedata.com/resource/pubmed/chemical/Heterocyclic Compounds, 3-Ring,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/SDX 308,
http://linkedlifedata.com/resource/pubmed/chemical/TCF Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0887-6924
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pubmed:author |
pubmed-author:AndersonK CKC,
pubmed-author:CarrascoD RDR,
pubmed-author:ChauhanDD,
pubmed-author:HideshimaTT,
pubmed-author:IkedaHH,
pubmed-author:KiziltepeTT,
pubmed-author:NeriPP,
pubmed-author:OcioE MEM,
pubmed-author:OkawaYY,
pubmed-author:PodarKK,
pubmed-author:RajoPP,
pubmed-author:RichardsonP GPG,
pubmed-author:SukhdeoKK,
pubmed-author:VallesPP,
pubmed-author:YasuiHH
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pubmed:issnType |
Print
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
535-40
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17268521-Antineoplastic Agents,
pubmed-meshheading:17268521-Apoptosis,
pubmed-meshheading:17268521-Cell Line, Tumor,
pubmed-meshheading:17268521-Cysteine Proteinase Inhibitors,
pubmed-meshheading:17268521-Drug Resistance, Neoplasm,
pubmed-meshheading:17268521-Drug Screening Assays, Antitumor,
pubmed-meshheading:17268521-Etodolac,
pubmed-meshheading:17268521-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17268521-Heterocyclic Compounds, 3-Ring,
pubmed-meshheading:17268521-Humans,
pubmed-meshheading:17268521-Insulin-Like Growth Factor I,
pubmed-meshheading:17268521-Interleukin-6,
pubmed-meshheading:17268521-Multiple Myeloma,
pubmed-meshheading:17268521-Neoplasm Proteins,
pubmed-meshheading:17268521-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:17268521-Signal Transduction,
pubmed-meshheading:17268521-TCF Transcription Factors,
pubmed-meshheading:17268521-beta Catenin
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pubmed:year |
2007
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pubmed:articleTitle |
Novel etodolac analog SDX-308 (CEP-18082) induces cytotoxicity in multiple myeloma cells associated with inhibition of beta-catenin/TCF pathway.
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pubmed:affiliation |
Jerome Lipper Multiple-Myeloma Center, Department of Medical-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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