Journal article
DiOC2(3) is not a substrate for multidrug resistance protein (MRP)‐mediated drug efflux
Cytometry (New York, N.Y.), Vol.25(1), pp.14-20
09/01/1996
DOI: 10.1002/(SICI)1097-0320(19960901)25:1<14::AID-CYTO2>3.0.CO;2-E
Abstract
Multidrug resistance (MDR) is often related to expression of P‐glycoprotein (Pgp) or Multidrug Resistance Protein (MRP). Pgp‐mediated MDR can be evaluated by determining cellular retention of fluorescent substrates by flow cytometry. This study determined if agents used to evaluate Pgp function also can be used to evaluate MRP function. Cellular retention of doxorubicin (Dox), Rhodamine‐123 (Rh‐123), and 3,3′‐diethyloxacarbocyanine iodide (DiOC2(3)) were studied in MRP‐expressing cell lines (HL60/Adr and HT1080/DR4), whereas a Pgp expressing cell line (A2780/Dx5) served as a positive control. Overexpression of Pgp correlated inversely with retention of Dox, Rh‐123, and DiOC2(3); however, under identical experimental conditions (1 h reincubation in drug‐free medium), no retention difference of the three agents was detected between parental and MRP‐expressing resistant cells. Upon extending the reincubation time to 4 h, an efflux of Rh‐123 and Dox in the resistant lines became apparent and even more pronounced after 24 h; however, still no efflux was detectable for DiOC2(3). Incubation of the cells with a modulator of MDR, PAK‐104P, negated the observed drug efflux in Pgp and MRP expressing cells, which correlated with increased sensitivity of the MDR lines to doxorubicin. Thus both Dox and Rh‐123 can be used to evaluate MRP‐function, but DiOC2(3) can not. © 1996 Wiley‐Liss, Inc.
Details
- Title: Subtitle
- DiOC2(3) is not a substrate for multidrug resistance protein (MRP)‐mediated drug efflux
- Creators
- Hans Minderman - Roswell Park Cancer InstituteUdo Vanhoefer - Department of Internal Medicine, West German Cancer Center, University of Essen, Essen, GermanyKaroly Toth - Roswell Park Cancer InstituteMing‐Biao YinM. Denice Minderman - Roswell Park Cancer InstituteCarol Wrzosek - Roswell Park Cancer InstituteMarilyn L. Slovak - City Of Hope National Medical CenterYoucef M. Rustum - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Cytometry (New York, N.Y.), Vol.25(1), pp.14-20
- Publisher
- Wiley‐Liss, Inc
- DOI
- 10.1002/(SICI)1097-0320(19960901)25:1<14::AID-CYTO2>3.0.CO;2-E
- ISSN
- 0196-4763
- eISSN
- 1097-0320
- Number of pages
- 7
- Grant note
- American Cancer Society (DHP‐115) West German Cancer Center
- Language
- English
- Date published
- 09/01/1996
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359915002771
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