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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0006772,
umls-concept:C0007634,
umls-concept:C0013089,
umls-concept:C0040979,
umls-concept:C0085752,
umls-concept:C0178539,
umls-concept:C0282564,
umls-concept:C0332325,
umls-concept:C0333117,
umls-concept:C0443199,
umls-concept:C0596402,
umls-concept:C0596978,
umls-concept:C1280500,
umls-concept:C1999216
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pubmed:issue |
11
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pubmed:dateCreated |
1984-11-28
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pubmed:abstractText |
Calmodulin inhibitors enhance cytotoxic effects of doxorubicin (DOX) in DOX-resistant (P388/DOX) P388 mouse leukemia cells by increasing cellular accumulation and retention of drug. In P388/DOX cells treated for 3 hr, cytotoxic effects (based on colony formation in soft agar) of daunorubicin (DAU) in the presence of trifluoperazine (TFP) were DAU concentration-dependent and enhanced 2- to 100-fold. Additionally, in the presence of TFP, on a molar basis, equitoxic doses of DAU were 4-fold lower than DOX for P388/DOX cells. However, in P388/DOX cells treated for 3 hr with other anthracyclines, except for a slight enhancement in the cytotoxic effects of aclacinomycin A (ACM) with TFP, colony formation in soft agar of cells treated with N-trifluoroacetyladriamycin-14-valerate (AD32) and N-trifluoroacetyladriamycin were similar in the absence and presence of TFP. In DOX-sensitive (P388/S) P388 mouse leukemia cells treated for 3 hr, some enhancement in the cytotoxic effects due to TFP were observed with DAU and DOX but not with ACM, AD32, or N-trifluoroacetyladriamycin. Although accumulation of ACM and AD32 in P388/S and P388/DOX cells was similar and unaffected by TFP, the retention of ACM but not AD32 was enhanced 1.5-fold only in TFP-treated P388/DOX cells. In contrast, DAU accumulation in P388/S cells was 4-fold higher than in similarly treated P388/DOX cells, and the 2- and 4-fold increase due to TFP in the accumulation and retention, respectively, of DAU in P388/DOX cells was not observed in P388/S cells. Results from this study indicate that in P388/DOX cells, the calmodulin inhibitor TFP is more effective with DAU than DOX, significantly less effective with ACM, and ineffective with AD32 and N-trifluoroacetyladriamycin.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5056-61
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:6488165-Animals,
pubmed-meshheading:6488165-Biological Transport,
pubmed-meshheading:6488165-Cell Survival,
pubmed-meshheading:6488165-Daunorubicin,
pubmed-meshheading:6488165-Dose-Response Relationship, Drug,
pubmed-meshheading:6488165-Doxorubicin,
pubmed-meshheading:6488165-Drug Resistance,
pubmed-meshheading:6488165-Kinetics,
pubmed-meshheading:6488165-Leukemia, Experimental,
pubmed-meshheading:6488165-Leukemia P388,
pubmed-meshheading:6488165-Mice,
pubmed-meshheading:6488165-Trifluoperazine
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pubmed:year |
1984
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pubmed:articleTitle |
Differential effect of the calmodulin inhibitor trifluoperazine on cellular accumulation, retention, and cytotoxicity of anthracyclines in doxorubicin (adriamycin)-resistant P388 mouse leukemia cells.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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