Linked Life Data

15176077

Source:http://linkedlifedata.com/resource/pubmed/id/15176077

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-6-3
pubmed:abstractText
The objective of this investigation was to evaluate the effects of two dietary isothiocyanates (ITCs), benzyl- (BITC) and phenethyl isothiocyanate (PEITC), and one synthetic ITC, alpha-naphthyl isothiocyanate (1-NITC), on the P-glycoprotein (P-gp)- and multidrug-resistance protein 1 (MRP1)-mediated efflux of daunomycin (DNM), determine whether PEITC is a substrate of P-gp and/or MRP1, and elucidate the mechanism(s) involved in the inhibition of transport. BITC, PEITC, and 1-NITC significantly increased the 2-h accumulation of DNM in MCF-7/ADR (P-gp overexpression), PANC-1 (MRP1 overexpression), and human colon adenocarcinoma Caco-2 cells (except for 1-NITC). The accumulation of (14)C-PEITC was not changed in Caco-2, human breast cancer MDA435/LCC6 and MDA435/LCC6MDR1 (P-gp overexpression) cells in the absence and presence of the P-gp inhibitor verapamil, but significantly increased with the MRP inhibitor MK571 in PANC-1 cells. The isocyanate and amine metabolites had no effect on DNM accumulation in any cell line. After 2- and 24-h ITC treatments, cellular concentrations of glutathione (GSH) in PANC-1 and Caco-2 cells were depleted by BITC and PEITC, but not by 1-NITC; glutathione-S-transferase activity exhibited small changes. Our results suggest that (1) BITC, PEITC, and 1-NITC inhibit the P-gp- and MRP1-mediated efflux of DNM; (2) PEITC and/or its conjugates do not represent P-gp substrates; (3) BITC and PEITC, but not 1-NITC, inhibit MRP1 through the depletion of intracellular GSH, which acts as a cosubstrate for DNM efflux via MRP1; and (4) PEITC and/or its conjugates are MRP1 substrates so binding interactions with DNM represent a second potential mechanism involved in MRP1 inhibition.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3549
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1901-1911, 2004
pubmed:issnType
Print
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1901-11
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Effects of benzyl-, phenethyl-, and alpha-naphthyl isothiocyanates on P-glycoprotein- and MRP1-mediated transport.
pubmed:affiliation
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 517 Hochstetter Hall, 14260, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't