Linked Life Data

12824882

Source:http://linkedlifedata.com/resource/pubmed/id/12824882

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-6-25
pubmed:abstractText
STI571, an Abl-specific tyrosine kinase inhibitor, selectively kills Bcr-Abl-containing cells in vitro and in vivo. However, some chronic myelogenous leukemia (CML) cell lines are resistant to STI571. We evaluated whether STI571 interacts with P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1), and examined the effect of agents that reverse multidrug resistance (MDR) on the resistance to SI571 in MDR cells. STI571 inhibited the [(125)I]azidoagosterol A-photolabeling of P-gp, but not that of MRP1. K562/MDR cells that overexpress P-gp were 3.67 times more resistant to STI571 than the parental Philadelphia-chromosome-positive (Ph +) CML K562 cells, and this resistance was most effectively reversed by cepharanthine among the tested reversing agents. The concentration of STI571 required to completely inhibit tyrosine phosphorylation in K562/MDR cells was about 3 times higher than that in K562 cells, and cepharanthine abolished the difference. In KB-G2 cells that overexpress P-gp, but not Bcr-Abl, 2.5 micro M STI571 partly reversed the resistance to vincristine (VCR), paclitaxel, etoposide (VP-16) and actinomycin D (ACD) but not to Adriamycin (ADM) or colchicine. STI571 increased the accumulation of VCR, but not that of ADM in KB-G2 cells. STI571 did not reverse resistance to any agent in KB/MRP cells that overexpress MRP1. These findings suggest that STI571 is a substrate for P-gp, but is less efficiently transported by P-gp than VCR, and STI571 is not a substrate for MRP1. Among the tested reversing agents that interact with P-gp, cepharanthine was the most effective agent for the reversal of the resistance to STI571 in K562/MDR cells. Furthermore, STI571 itself was a potent reversing agent for MDR in P-gp-expressing KB-G2 cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1347-9032
pubmed:author
pubmed:issnType
Print
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
557-63
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12824882-Antineoplastic Agents, pubmed-meshheading:12824882-Cell Membrane, pubmed-meshheading:12824882-Cell Survival, pubmed-meshheading:12824882-Drug Resistance, Multiple, pubmed-meshheading:12824882-Drug Resistance, Neoplasm, pubmed-meshheading:12824882-Fusion Proteins, bcr-abl, pubmed-meshheading:12824882-Humans, pubmed-meshheading:12824882-K562 Cells, pubmed-meshheading:12824882-KB Cells, pubmed-meshheading:12824882-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:12824882-Leukotrienes, pubmed-meshheading:12824882-Multidrug Resistance-Associated Proteins, pubmed-meshheading:12824882-P-Glycoprotein, pubmed-meshheading:12824882-Phosphorylation, pubmed-meshheading:12824882-Photoaffinity Labels, pubmed-meshheading:12824882-Piperazines, pubmed-meshheading:12824882-Pyrimidines, pubmed-meshheading:12824882-Tyrosine
pubmed:year
2003
pubmed:articleTitle
Reversal of the resistance to STI571 in human chronic myelogenous leukemia K562 cells.
pubmed:affiliation
Department of Cancer Chemotherapy, Institute for Cancer Research, Kagoshima University, Kagoshima 890-8520, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't