Linked Life Data

14713364

Source:http://linkedlifedata.com/resource/pubmed/id/14713364

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-1-9
pubmed:abstractText
Multidrug resistance (MDR) represents a major problem in cancer chemotherapy. P-glycoprotein (P-gp), the drug efflux pump that mediates this resistance, can be inhibited by compounds with a variety of pharmacological functions, thus circumventing the MDR phenotype. The present study was performed to evaluate a unique MDR-reversal feature of a bisbenzylisoquinoline alkaloid tetrandrine (TET) in a P-gp expressing MOLT-4 MDR line (MOLT-4/DNR) established in our laboratory. Cell viability was determined by an MTT assay. P-gp function was characterized by determining the Rh123 accumulation/efflux capacity. P-gp overexpression in resistant MOLT-4/DNR cells was confirmed by flow cytometry analysis after staining with phycoerythrin-conjugated anti-P-gp monoclonal antibody 17F9. Compared to ciclosporin A (CsA), TET exhibited stronger activity to reverse drug resistance to daunorubicin (DNR), vinblastine (VLB) and doxorubicin (DOX) in MOLT-4/DNR cells. TET showed no cytotoxic effects on parental MOLT-4 cells lacking P-gp expression or on the resistant MOLT-4/DNR cells. TET modulated DNR cytotoxicity even after it was washed with the medium for 24 h, while CsA almost completely lost its reversal capability 24 h after washing. TET and CsA similarly increased the accumulation of Rh123 in resistant MOLT-4/DNR cells. However, TET inhibited Rh123 efflux from resistant cells even after washing with the medium, while CsA rapidly lost its ability to inhibit Rh123 efflux after washing. The current study suggests that TET enhances the cytotoxicity of anticancer drugs in the P-gp expressing MDR cell line by modulating P-gp in a different manner to the well-known P-gp inhibitor CsA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3573
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1531-7
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Persistent reversal of P-glycoprotein-mediated daunorubicin resistance by tetrandrine in multidrug-resistant human T lymphoblastoid leukemia MOLT-4 cells.
pubmed:affiliation
Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
pubmed:publicationType
Journal Article