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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2005-8-24
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pubmed:abstractText |
Expression of the multidrug resistance (MDR) transporter P-glycoprotein (P-gp) has been demonstrated to be regulated by hypoxia-inducible factor-1alpha (HIF-1alpha) and inhibited by intracellular reactive oxygen species (ROS). Herein, P-gp and HIF-1alpha expression were investigated in multicellular prostate tumor spheroids overexpressing the ROS-generating enzyme Nox-1 in comparison to the mother cell line DU-145. In Nox-1-overexpressing tumor spheroids (DU-145Nox1) generation of ROS as well as expression of Nox-1 was significantly increased as compared to DU-145 tumor spheroids. ROS generation was significantly inhibited in the presence of the NADPH-oxidase antagonists diphenylen-iodonium chloride (DPI) and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF). Albeit growth kinetic of DU-145Nox1 tumor spheroids was decreased as compared to DU-145 spheroids, elevated expression of Ki-67 was observed indicating increased cell cycle activity. In DU-145Nox1 tumor spheroids, expression of HIF-1alpha as well as P-gp was significantly decreased as compared to DU-145 spheroids, which resulted in an increased retention of the anticancer agent doxorubicin. Pretreatment with the free radical scavengers vitamin E and vitamin C increased the expression of P-gp as well as HIF-1alpha in Nox-1-overexpressing cells, whereas no effect of free radical scavengers was observed on mdr-1 mRNA expression. In summary, the data of the present study demonstrate that the development of P-gp-mediated MDR is abolished under conditions of elevated ROS levels, suggesting that the MDR phenotype can be circumvented by modest increase of intracellular ROS generation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-(2-aminoethyl)benzenesulfonylfluor...,
http://linkedlifedata.com/resource/pubmed/chemical/Ascorbic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Biphenyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Free Radical Scavengers,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Multidrug Resistance-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/NOX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Onium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfones,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin E,
http://linkedlifedata.com/resource/pubmed/chemical/diphenyliodonium
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0014-5793
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
579
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4541-4549
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pubmed:dateRevised |
2006-6-27
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pubmed:meshHeading |
pubmed-meshheading:16083877-Ascorbic Acid,
pubmed-meshheading:16083877-Biphenyl Compounds,
pubmed-meshheading:16083877-Cell Line, Tumor,
pubmed-meshheading:16083877-Drug Resistance, Multiple,
pubmed-meshheading:16083877-Free Radical Scavengers,
pubmed-meshheading:16083877-Humans,
pubmed-meshheading:16083877-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:16083877-Male,
pubmed-meshheading:16083877-Multidrug Resistance-Associated Proteins,
pubmed-meshheading:16083877-NADPH Oxidase,
pubmed-meshheading:16083877-Onium Compounds,
pubmed-meshheading:16083877-P-Glycoprotein,
pubmed-meshheading:16083877-Prostatic Neoplasms,
pubmed-meshheading:16083877-Reactive Oxygen Species,
pubmed-meshheading:16083877-Spheroids, Cellular,
pubmed-meshheading:16083877-Sulfones,
pubmed-meshheading:16083877-Transcription Factors,
pubmed-meshheading:16083877-Vitamin E
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pubmed:year |
2005
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pubmed:articleTitle |
Reactive oxygen species-linked regulation of the multidrug resistance transporter P-glycoprotein in Nox-1 overexpressing prostate tumor spheroids.
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pubmed:affiliation |
Department of Cell Biology, GKSS Research Center, Teltow, Germany.
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pubmed:publicationType |
Journal Article
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