| Effect of organic isothiocyanates on the P-glycoprotein- and MRP1-mediated transport of daunomycin and vinblastine. | |
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MedLine Citation:
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PMID: 12425469 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Organic isothiocyanates (ITCs), or mustard oils, are non-nutrient components present in the diet, especially in cruciferous vegetables. The purpose of this investigation was to examine the effect of ITCs on P-glycoprotein (P-gp)- and multidrug resistance-associated Protein (MRP1)-mediated transport in multidrug resistant (MDR) human cancer cell lines. METHODS: The direct effect of ITCs on the 2-h cellular accumulation of daunomycin (DNM) and vinblastine (VBL), substrates for both P-gp and MRP1, were measured in sensitive and resistant MCF-7 cells and in PANC-1 cells. Resistant MCF-7 cells (MCF-7/ADR) overexpress P-gp whereas PANC-1 cells overexpress MRP1. The following compounds were evaluated: allyl-, benzyl-(BITC), hexyl-, phenethyl-(PEITC), phenyl-, 1-naphthyl-(NITC), phenylhexyl-, phenylpropyl-, and phenylbutyl-ITC, sulforaphane, erucin, and erysolin. RESULTS: NITC significantly increased the accumulation of DNM and VBL in both resistant cell lines, but had no effect on DNM accumulation in sensitive MCF-7 cells. VBL accumulation in resistant MCF-7 cells was increased 40-fold by NITC whereas that in PANC-1 cells was increased 5.5-fold. Significant effects on the accumulation of DNM and VBL in resistant MCF-7 cells were also observed with benzyl-isothiocyanate whereas PEITC, erysolin, phenylhexyl-ITC, and phenylbutyl-ITC increased the accumulation of DNM and/or VBL in PANC-1 cells. Overall, the inhibitory activities of these compounds in MCF-7 cells and PANC-1 cells were significantly correlated (r2 = 0.77 and 0.86 for DNM and VBL, respectively). Significant effects on accumulation were generally observed with the ITCs at 50 microM concentrations, but not at 10 microM concentrations. CONCLUSIONS: One strategy to enhance the effectiveness of cancer chemotherapy is to reverse the MDR phenomena. Our results indicate that certain dietary ITCs inhibit the P-gp- and the MRP1-mediated efflux of DNM and VBL in MDR cancer cells and suggest the potential for diet-drug interactions. |
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Authors:
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Elaine Tseng; Amrita Kamath; Marilyn E Morris |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Pharmaceutical research Volume: 19 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 2002 Oct |
Date Detail:
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Created Date: 2002-11-11 Completed Date: 2003-04-24 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: United States |
Other Details:
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Languages: eng Pagination: 1509-15 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Biological Transport
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physiology Daunorubicin / pharmacokinetics* Humans Isothiocyanates / pharmacology* P-Glycoprotein / metabolism* Tumor Cells, Cultured Vinblastine / pharmacokinetics* |
| Chemical | |
Reg. No./Substance:
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0/Isothiocyanates; 0/P-Glycoprotein; 20830-81-3/Daunorubicin; 865-21-4/Vinblastine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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