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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
1998-11-9
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pubmed:abstractText |
We have examined the cytotoxic effects of cyclic adenosine-3', 5'-monophosphate (cAMP) derivatives on multiple myeloma cells lines and determined that the 8-Chloro substituted derivative (8Cl-cAMP) is one of the most potent. We report here that 8Cl-cAMP is cytotoxic to both steroid sensitive and insensitive myeloma cells with a half maximal concentration of approximately 3 micromol/L. 8Cl-cAMP toxicity in myeloma cells is dependent on phosphodiesterase activity in the serum of cell culture medium. A metabolite of 8Cl-cAMP, 8-Chloro-adenosine (8Cl-AD), kills myeloma cells as effectively as 8Cl-cAMP. Adenosine deaminase (ADA) converts 8Cl-AD into 8Cl-inosine and abrogates the cytotoxic effects of 8Cl-cAMP, 8Cl-AMP, and 8Cl-AD, as does 5-(p-Nitrobenzyl)-6-Thio-Inosine (NBTI), an inhibitor of nucleoside uptake. These data suggest that 8Cl-cAMP must be converted to 8Cl-AD and that 8Cl-AD is the compound that enters the cell. Contrary to glucocorticoid-mediated cell death in myeloma cells, the pathway of 8Cl-AD-mediated cell death appears to be independent of interleukin-6 (IL-6) actions. Although the exact mode of action for this agent is currently unknown, its ability to kill steroid sensitive and insensitive multiple myeloma cells in an IL-6 independent fashion may offer exciting new therapeutic options.
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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 |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/2-Chloroadenosine,
http://linkedlifedata.com/resource/pubmed/chemical/4-nitrobenzylthioinosine,
http://linkedlifedata.com/resource/pubmed/chemical/8-Bromo Cyclic Adenosine...,
http://linkedlifedata.com/resource/pubmed/chemical/8-chloro-cyclic adenosine...,
http://linkedlifedata.com/resource/pubmed/chemical/8-chloroadenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Deaminase,
http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Diester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Prodrugs,
http://linkedlifedata.com/resource/pubmed/chemical/Thioinosine
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 1998 by The American Society of Hematology.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
92
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2893-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9763575-1-Methyl-3-isobutylxanthine,
pubmed-meshheading:9763575-2-Chloroadenosine,
pubmed-meshheading:9763575-8-Bromo Cyclic Adenosine Monophosphate,
pubmed-meshheading:9763575-Adenosine Deaminase,
pubmed-meshheading:9763575-Animals,
pubmed-meshheading:9763575-Antimetabolites, Antineoplastic,
pubmed-meshheading:9763575-Apoptosis,
pubmed-meshheading:9763575-Biological Transport,
pubmed-meshheading:9763575-Biotransformation,
pubmed-meshheading:9763575-Cattle,
pubmed-meshheading:9763575-Culture Media,
pubmed-meshheading:9763575-Drug Resistance, Neoplasm,
pubmed-meshheading:9763575-Drug Screening Assays, Antitumor,
pubmed-meshheading:9763575-Humans,
pubmed-meshheading:9763575-Interleukin-6,
pubmed-meshheading:9763575-Multiple Myeloma,
pubmed-meshheading:9763575-Phosphoric Diester Hydrolases,
pubmed-meshheading:9763575-Prodrugs,
pubmed-meshheading:9763575-Thioinosine,
pubmed-meshheading:9763575-Tumor Cells, Cultured
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pubmed:year |
1998
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pubmed:articleTitle |
8Cl-cAMP cytotoxicity in both steroid sensitive and insensitive multiple myeloma cell lines is mediated by 8Cl-adenosine.
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pubmed:affiliation |
Lurie Comprehensive Cancer Center and Department of Medicine, Northwestern University, Chicago, IL, USA. r-halgren@nwu.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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