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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1987-3-26
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pubmed:abstractText |
Previous investigations have shown that untargeted liposomes, in which methotrexate is anchored to the lipid bilayers as methotrexate-gamma-dimyristoylphosphatidylethanolamine (methotrexate-gamma-DMPE), can inhibit in vitro cell proliferation. To test the possibility that this inhibition may involve extracellular metabolism of methotrexate-gamma-DMPE, we have degraded it chemically (dilute alkali) or enzymatically (phospholipase A2, phospholipase C, phospholipase C plus phosphatase), and assayed the products using human lymphoblastoid T cells or a subline that has a defective methotrexate transport system. Neither methotrexate-gamma-(1-myristoyl)-glycerophosphorylethanolamine, methotrexate-gamma-glycerophosphorylethanolamine, methotrexate-gamma-phosphorylethanolamine, nor methotrexate-gamma-ethanolamine resemble methotrexate-gamma-DMPE sensitized liposomes or the free derivative in their ability to block tritiated deoxyuridine incorporation into DNA. When added extracellularly, these putative metabolites manifest a higher ID50 concentration and/or, unlike the liposomes or unincorporated methotrexate-gamma-DMPE, utilize the methotrexate transport system to enter cells. Additionally, we have synthesized methotrexate-gamma-dihexadecylphosphatidylethanolamine and methotrexate-gamma-hexadecylphosphorylethanolamine, analogs of methotrexate-gamma-DMPE that cannot be hydrolyzed by phospholipases A2, C and D; liposomes prepared with these derivatives are markedly less potent cytotoxic agents than methotrexate-gamma-DMPE sensitized liposomes. All together, these results are consistent with the conclusion that methotrexate-gamma-DMPE must undergo intracellular metabolism to exert optimal inhibition; they also bear on possible mechanisms by which methotrexate-gamma-DMPE may enter cells.
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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/Deoxyuridine,
http://linkedlifedata.com/resource/pubmed/chemical/Liposomes,
http://linkedlifedata.com/resource/pubmed/chemical/Methotrexate,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylethanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/methotrexate-gamma-1,2-dimyristoylph...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
917
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
211-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:3492219-Cell Division,
pubmed-meshheading:3492219-Cell Line,
pubmed-meshheading:3492219-Deoxyuridine,
pubmed-meshheading:3492219-Humans,
pubmed-meshheading:3492219-Liposomes,
pubmed-meshheading:3492219-Methotrexate,
pubmed-meshheading:3492219-Phosphatidylethanolamines,
pubmed-meshheading:3492219-T-Lymphocytes
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pubmed:year |
1987
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pubmed:articleTitle |
Inhibition of cell proliferation by putative metabolites and non-degradable analogs of methotrexate-gamma-dimyristoylphosphatidylethanolamine.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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