Linked Life Data

19806783

Source:http://linkedlifedata.com/resource/pubmed/id/19806783

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11-12
pubmed:dateCreated
2009-10-7
pubmed:abstractText
The purpose of this study is to examine the effects of doxazosin, an alpha-adrenoceptor antagonist, on P-glycoprotein/MDR1-mediated multidrug resistance (MDR) and the transport of anticancer drugs. The effects of doxazosin, prazosin, and terazosin on MDR1-mediated MDR were assessed in human cervical carcinoma HeLa cells and the MDR1-overexpressing derivative Hvrl00-6, established by stepwise increases of the vinblastine concentration in the culture medium. The effects of doxazosin on the transcellular transport and intracellular accumulation of [3H]vinblastine, [3H]daunorubicin, and [3H]digoxin, all MDR1 substrates, were evaluated using LLC-GA5-COL150 cell monolayers, established by transfection of human MDR1 cDNA into porcine kidney epithelial LLC-PK1 cells. The sensitivity to vinblastine and paclitaxel of Hvrl00-6 cells was increased at 3.4- and 17.5-fold, respectively, by the addition of 1 microM doxazosin, whereas prazosin and terazosin had weaker or no such effects. Prazosin at 1 microM had a reversal effect on the sensitivity to vinblastine, whereas terazosin had no effect. In transport experiments, doxazosin concentration dependently increased the apical-to-basal transport of radiolabeled drugs in LLC-GA5-COL150 cells, but did not show remarkable effects on the basal-to-apical transport. In addition, doxazosin restored the intracellular accumulation in a concentration-dependent manner in LLC-GA5-COL150 cells. Doxazosin may partly reverse MDR by inhibiting MDR1-mediated transport, making it a candidate lead compound in the development of a reversing agent for MDR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/ABCB1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/ABCG2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters, http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Daunorubicin, http://linkedlifedata.com/resource/pubmed/chemical/Digoxin, http://linkedlifedata.com/resource/pubmed/chemical/Doxazosin, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein, http://linkedlifedata.com/resource/pubmed/chemical/Prazosin, http://linkedlifedata.com/resource/pubmed/chemical/Terazosin, http://linkedlifedata.com/resource/pubmed/chemical/Vinblastine
pubmed:status
MEDLINE
pubmed:issn
0965-0407
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
527-33
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Effects of alpha-adrenoceptor antagonist doxazosin on MDR1-mediated multidrug resistance and transcellular transport.
pubmed:affiliation
Frontier Education Center, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. takara@gm.himeji-du.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't