Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
1990-11-8
|
| pubmed:abstractText |
Cremophor EL (polyoxyethylene castor oil) and Tween 80, used as solvents for cyclosporin A and VP-16, respectively, were found to reverse the multidrug resistant (MDR) phenotype. In daunorubicin (DNR) resistant Ehrlich ascites tumor cells (EHR2/DNR+), both solvents at percentages of 0.01% (v/v) enhanced DNR accumulation to sensitive levels. Cremophor EL and Tween 80 did not influence DNR accumulation in drug-sensitive cells (EHR2). The concentration of cyclosporin A alone that enhanced DNR accumulation in EHR2/DNR+ cells to sensitive levels was 5 micrograms/mL whereas 0.2 micrograms/mL of cyclosporin A dissolved in 0.001% (v/v) Cremophor EL enhanced DNR accumulation to sensitive levels, thus indicating synergy between Cremophor EL and cyclosporin A. Cyclosporin A had a negligible effect on DNR accumulation in the drug-sensitive cells. In clonogenic assays, the LD10 of DNR was 1 microM in EHR2/DNR+ cells. Combining 1 microM DNR with non-toxic amounts of Cremophor EL (0.001% and 0.002%, v/v) potentiated the cytotoxicity of DNR and resulted in a cell kill of 77% and 86%, respectively, in the resistant cells. In non-toxic amounts, CrEL and Tween 80 acted synergistically with reduced concentrations of verapamil, resulting in DNR accumulation approaching close to the sensitive level. Azidopine photoaffinity labeling of P-glycoprotein in plasma membrane vesicles from EHR2/DNR+ cells was inhibited 100% and 80%, by 0.003% (v/v) Cremophor EL or Tween 80, respectively. These data permit the conclusion that non-toxic amounts of CrEL and Tween 80 modulated DNR resistance by raising intracellular DNR levels, due to their abilities to bind to the plasma membrane P-glycoprotein.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Azides,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporins,
http://linkedlifedata.com/resource/pubmed/chemical/Daunorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Dihydropyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Glycerol,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Polysorbates,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/Verapamil,
http://linkedlifedata.com/resource/pubmed/chemical/azidopine,
http://linkedlifedata.com/resource/pubmed/chemical/cremophor EL
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0955-3541
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
2
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
297-303
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:1976341-Animals,
pubmed-meshheading:1976341-Azides,
pubmed-meshheading:1976341-Carcinoma, Ehrlich Tumor,
pubmed-meshheading:1976341-Cyclosporins,
pubmed-meshheading:1976341-Daunorubicin,
pubmed-meshheading:1976341-Dihydropyridines,
pubmed-meshheading:1976341-Drug Resistance,
pubmed-meshheading:1976341-Drug Synergism,
pubmed-meshheading:1976341-Drug Therapy, Combination,
pubmed-meshheading:1976341-Glycerol,
pubmed-meshheading:1976341-Humans,
pubmed-meshheading:1976341-Intracellular Membranes,
pubmed-meshheading:1976341-Membrane Glycoproteins,
pubmed-meshheading:1976341-P-Glycoprotein,
pubmed-meshheading:1976341-Polysorbates,
pubmed-meshheading:1976341-Tritium,
pubmed-meshheading:1976341-Tumor Cells, Cultured,
pubmed-meshheading:1976341-Verapamil
|
| pubmed:year |
1990
|
| pubmed:articleTitle |
The solvents cremophor EL and Tween 80 modulate daunorubicin resistance in the multidrug resistant Ehrlich ascites tumor.
|
| pubmed:affiliation |
Department of Medicine, Finsen Institute-Rigshospitalet, Copenhagen, Denmark.
|
| pubmed:publicationType |
Journal Article
|