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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
23
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pubmed:dateCreated |
2004-12-2
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pubmed:abstractText |
2-(8-Hydroxy-6-methoxy-1-oxo-1Eta-2-benzopyran-3-yl)propionic acid (NM-3) is a small molecule isocoumarin derivative that has recently entered clinical trials as an orally bioavailable anticancer agent. NM-3 induces lethality of human carcinoma cells by both apoptotic and nonapoptotic mechanisms and potentiates the effects of cytotoxic chemotherapeutic agents. The present studies have evaluated the effects of NM-3 on human multiple myeloma (MM) cells. The results demonstrate that NM-3 potentiates dexamethasone-induced killing of both dexamethasone-sensitive MM1.S and dexamethasone-resistant RPMI8226 and U266 MM cells. We show that NM-3 enhances dexamethasone-induced release of the mitochondrial apoptogenic factors cytochrome c and Smac/DIABLO. The results also demonstrate that NM-3 enhances dexamethasone-induced activation of the intrinsic caspase-9->caspase-3 apoptotic pathway. In concert with these results, NM-3 potentiates dexamethasone-induced apoptosis of MM1.S cells. Moreover, NM-3 acts synergistically with dexamethasone in inducing apoptosis of the dexamethasone-resistant RPMI8226 and U266 MM cells. These findings indicate that NM-3 may be effective in combination with dexamethasone in the treatment of MM.
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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/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Coumarins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/DIABLO protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Isocoumarins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/isocoumarin NM-3
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
64
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8512-6
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15574755-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:15574755-Apoptosis,
pubmed-meshheading:15574755-Carrier Proteins,
pubmed-meshheading:15574755-Caspase 3,
pubmed-meshheading:15574755-Caspase 9,
pubmed-meshheading:15574755-Caspases,
pubmed-meshheading:15574755-Cell Line, Tumor,
pubmed-meshheading:15574755-Coumarins,
pubmed-meshheading:15574755-Cytochromes c,
pubmed-meshheading:15574755-Dexamethasone,
pubmed-meshheading:15574755-Drug Resistance, Neoplasm,
pubmed-meshheading:15574755-Drug Synergism,
pubmed-meshheading:15574755-Enzyme Activation,
pubmed-meshheading:15574755-Humans,
pubmed-meshheading:15574755-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15574755-Isocoumarins,
pubmed-meshheading:15574755-Mitochondria,
pubmed-meshheading:15574755-Mitochondrial Proteins,
pubmed-meshheading:15574755-Multiple Myeloma,
pubmed-meshheading:15574755-Reactive Oxygen Species
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pubmed:year |
2004
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pubmed:articleTitle |
2-(8-Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl)propionic acid, a small molecule isocoumarin, potentiates dexamethasone-induced apoptosis of human multiple myeloma cells.
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pubmed:affiliation |
ILEX Products, Inc., Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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