|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
33
|
|
pubmed:dateCreated |
2006-8-14
|
|
pubmed:abstractText |
The new glutathione S-transferase inhibitor 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) is cytotoxic toward P-glycoprotein-overexpressing tumor cell lines, i.e. CEM-VBL10, CEM-VBL100, and U-2 OS/DX580. The mechanism of cell death triggered by NBDHEX has been deeply investigated in leukemia cell lines. Kinetic data indicate a similar NBDHEX membrane permeability between multidrug resistance cells and their sensitive counterpart revealing that NBDHEX is not a substrate of the P-glycoprotein export pump. Unexpectedly, this molecule promotes a caspase-dependent apoptosis that is unusual in the P-glycoprotein-overexpressing cells. The primary event of the apoptotic pathway is the dissociation of glutathione S-transferase P1-1 from the complex with c-Jun N-terminal kinase. Interestingly, leukemia MDR1-expressing cells show lower LC50 values and a higher degree of apoptosis and caspase-3 activity than their drug-sensitive counterparts. The increased susceptibility of the multidrug resistance cells toward the NBDHEX action may be related to a lower content of glutathione S-transferase P1-1. Given the low toxicity of NBDHEX in vivo, this compound may represent an attractive basis for the selective treatment of MDR1 P-glycoprotein-positive tumors.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
pubmed-author:CaccuriAnna MariaAM,
pubmed-author:CianfrigliaMaurizioM,
pubmed-author:CirioloMaria RosaMR,
pubmed-author:De MariaFrancescaF,
pubmed-author:DupuisMaria LuisaML,
pubmed-author:FedericiGiorgioG,
pubmed-author:FilomeniGiuseppeG,
pubmed-author:MolinariAgneseA,
pubmed-author:RicciGiorgioG,
pubmed-author:TombesiMarinaM,
pubmed-author:TurellaPaolaP
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
18
|
|
pubmed:volume |
281
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
23725-32
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:16769721-Acute Disease,
pubmed-meshheading:16769721-Antineoplastic Agents,
pubmed-meshheading:16769721-Apoptosis,
pubmed-meshheading:16769721-Biological Transport,
pubmed-meshheading:16769721-Caspases,
pubmed-meshheading:16769721-Cell Death,
pubmed-meshheading:16769721-Cell Line, Tumor,
pubmed-meshheading:16769721-Drug Resistance, Multiple,
pubmed-meshheading:16769721-Drug Resistance, Neoplasm,
pubmed-meshheading:16769721-Enzyme Inhibitors,
pubmed-meshheading:16769721-Glutathione Transferase,
pubmed-meshheading:16769721-Humans,
pubmed-meshheading:16769721-Kinetics,
pubmed-meshheading:16769721-Leukemia, T-Cell,
pubmed-meshheading:16769721-Mitochondria,
pubmed-meshheading:16769721-Oxadiazoles,
pubmed-meshheading:16769721-P-Glycoprotein,
pubmed-meshheading:16769721-Phenotype,
pubmed-meshheading:16769721-Piperazines
|
|
pubmed:year |
2006
|
|
pubmed:articleTitle |
A strong glutathione S-transferase inhibitor overcomes the P-glycoprotein-mediated resistance in tumor cells. 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) triggers a caspase-dependent apoptosis in MDR1-expressing leukemia cells.
|
|
pubmed:affiliation |
Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, 00133 Rome, Italy.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
