In vitro efficacy of known P-glycoprotein modulators compared to droloxifene E and Z: studies on a human T-cell leukemia cell line and their resistant variants.

Abstract:

:P-glycoprotein(P-gp)- related resistance is one of the major obstacles in treating leukemia patients. Therefore, it is of clinical interest to find new potential modulators and compare their P-gp-modulating efficacy. The present analysis investigated the influence of P-gp modulators, such as verapamil, tamoxifen, droloxifene E, droloxifene Z, SDZ PSC 833 (PSC 833) and dexniguldipine in a leukemic T-cell line (CCRF-CEM) and its P-gp-resistant counterparts (CCRF-CEM/ACT400 and CCRF-CEM/VCR1000). P-gp expression was assessed with an immunocytological technique using the monoclonal antibody 4E3.16. It was characterized as the percentage of P-gp positive cells and also expressed as a D value by using the Kolmogorov Smirnov statistic. The efficacy of P-gp modulators was determined with the rhodamine-123 accumulation test and the MTT test. An in vitro modulator concentration between 0.1 microM and 3 microM was determined, where no genuine antiproliferative effect was apparent. The modulators PSC 833 and dexniguldipine were the significant (p

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Nüssler V,Pelka-Fleisc R,Gieseler F,Hasmann M,Löser R,Gullis E,Stötzer O,Zwierzina H,Wilmanns W

doi

10.3109/10428199809057619

subject

Has Abstract

pub_date

1998-11-01 00:00:00

pages

589-97

issue

5-6

eissn

1042-8194

issn

1029-2403

journal_volume

31

pub_type

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