In vitro efficacy of known P-glycoprotein modulators compared to droloxifene E and Z: studies on a human T-cell leukemia cell line and its resistant variants (2023)

Nüssler, V., Pelka-Fleisc, R., Gieseler, F., Hasmann, M., Löser, R., Gullis, E., Stötzer, O., Zwierzina, H., & Wilmanns, W. (1998).In vitro efficacy of known P-glycoprotein modulators compared to droloxifene E and Z: studies on a human T-cell leukemia cell line and its resistant variants.leukemia and lymphoma,31(5-6), 589-597.https://doi.org/10.3109/10428199809057619

Nuessler, Volkmar ; Pelka-Fleisc, Renate; Gieseler, Franket al. /In vitro efficacy of known P-glycoprotein modulators compared to droloxifene E and Z: studies on a human T-cell leukemia cell line and its resistant variants. In:leukemia and lymphoma. 1998; Bd. 31, Nr. 5-6. pp. 589-597.

@article{0ed30e3510e34cd0884e88d88794f442,

title = "In vitro efficacy of known P-glycoprotein modulators versus droloxifene E and Z: studies in a human T-cell leukemia cell line and its resistant variants",

abstract = "P-glycoprotein (P-gp)-related resistance is one of the major obstacles in the treatment of leukemia patients. Therefore, it is of clinical interest to find new potential modulators and compare their P-gp modulating potency. The present analysis studied the influence of P-gp modulators such as verapamil, tamoxifen, droloxifen E, droloxifen Z, SDZ PSC 833 (PSC 833) and dexniguldipine in a leukemic T cell line (CCRF-CEM) and their P-gp-resistant counterparts (CCRF -CEM/ACT400 and CCRF-CEM/VCR1000).P-gp expression was assessed by an immunocytological technique using monoclonal antibody 4E3.16.It was characterized as percentage of P-gp positive cells and also expressed as D Value using Kolmogorov-Smirnov statistic The potency of P-gp modulators was determined using the rhodamine-123 accumulation test and the MTT test. A modulator concentration in vitro between 0.1 μM and 3 μM determined at which no real antiproliferative effect was detectable. The modulator PSC 833 and dexniguldipine were the significantly (p < C0.05) strongest chemosensitizers, followed by verapamil, droloxifene Z, tamoxifene and droloxifene E in descending order. In addition to the modulators PSC 833 and dexniguldipine, droloxifen Z in particular is a candidate for future ex-vivo and in-vivo studies. The main advantage of Droloxifen Z could be the low rate of expected side effects. This fact allows the use of a high dosage of Drol Z to achieve a relevant modulating effect in vivo and the use of this drug in combination with another modulator to achieve maximum efficacy with tolerable side effects.",

author = "Volkmar N{\"u}ssler and Renate Pelka-Fleisc and Frank Gieseler and Max Hasmann and Rainer L{\"o}ser and Edith Gullis and Oliver St{\"o}tzer and Heinz Zwierzina and Wolfgang Wilmanns" ,

year="1998",

doi = "10.3109/10428199809057619",

language="English",

volume = "31",

Pages="589--597",

Magazine = "Leukemia and Lymphoma",

issn = "1042-8194",

number="5-6",

}

Nüssler, V, Pelka-Fleisc, R, Gieseler, F, Hasmann, M, Löser, R, Gullis, E, Stötzer, O, Zwierzina, H & Wilmanns, W 1998, 'In vitro efficacy of known P-glycoprotein modulators compared to droloxifene E and Z: studies on a human T-cell leukemia cell line and its resistant variants',leukemia and lymphoma, Bd. 31, Nr. 5-6, p. 589-597.https://doi.org/10.3109/10428199809057619

In vitro efficacy of known P-glycoprotein modulators compared to droloxifene E and Z: studies on a human T-cell leukemia cell line and its resistant variants./ Nüssler, Volkmar; Pelka-Fleisc, Renate; Gieseler, Franket al.

In:leukemia and lymphoma, Bd. 31, Nr. 5–6, 1998, S. 589-597.

research result:contribution to the journal›newspaper article›Research›Peer-Review

YOU - TAG

T1 - In vitro efficacy of known P-glycoprotein modulators compared to droloxifene E and Z: studies in a human T-cell leukemia cell line and its resistant variants

AU - Nüssler, Volkmar

AU - Pelka meat, Renate

AU - Gieseler, Frank

AU - Hasmann, Max

AU - Solve, Rainer

AU - Gullis, Edith

AU - Stötzer, Oliver

AU - Game, Heinz

AU - Wilmanns, Wolfgang

PJ - 1998

J1 - 1998

N2-P-glycoprotein (P-gp)-related resistance is one of the main obstacles in the treatment of leukemia patients. Therefore, it is of clinical interest to find new potential modulators and compare their P-gp modulating potency. The present analysis investigated the influence of P-gp modulators such as verapamil, tamoxifen, droloxifen E, droloxifen Z, SDZ PSC 833 (PSC 833) and dexniguldipine in a leukemic T cell line (CCRF-CEM) and its P-gp -resistant ones counterparts (CCRF-CEM/ACT400 and CCRF-CEM/VCR1000). P-gp expression was assessed by an immunocytological technique using monoclonal antibody 4E3.16. It was characterized as percentage of P-gp positive cells and also expressed as a D value using Kolmogorov-Smirnov statistic. The potency of P-gp modulators was determined using the rhodamine 123 accumulation test and the MTT test. An in vitro modulator concentration between 0.1 μM and 3 μM was determined at which no real antiproliferative effect was detectable. The modulators PSC 833 and dexniguldipine were the most significant (p<C0.05) most potent chemosensitizers, followed by verapamil, droloxifen Z, tamoxifen, and droloxifen E in descending order. In addition to the modulators PSC 833 and dexniguldipine, droloxifen Z in particular is a candidate for future ex-vivo and in-vivo studies. The main advantage of Droloxifen Z could be the low rate of expected side effects. This fact allows the use of a high Drol Z dosage to achieve a relevant modulating effect in vivo and the use of this drug in combination with another modulator to achieve maximum efficacy with tolerable side effects.

AB - P-glycoprotein (P-gp)-related resistance is one of the major obstacles in the treatment of leukemia patients. Therefore, it is of clinical interest to find new potential modulators and compare their P-gp modulating potency. The present analysis investigated the influence of P-gp modulators such as verapamil, tamoxifen, droloxifen E, droloxifen Z, SDZ PSC 833 (PSC 833) and dexniguldipine in a leukemic T cell line (CCRF-CEM) and its P-gp -resistant ones counterparts (CCRF-CEM/ACT400 and CCRF-CEM/VCR1000). P-gp expression was assessed by an immunocytological technique using monoclonal antibody 4E3.16. It was characterized as percentage of P-gp positive cells and also expressed as a D value using Kolmogorov-Smirnov statistic. The potency of P-gp modulators was determined using the rhodamine 123 accumulation test and the MTT test. An in vitro modulator concentration between 0.1 μM and 3 μM was determined at which no real antiproliferative effect was detectable. The modulators PSC 833 and dexniguldipine were the most significant (p<C0.05) most potent chemosensitizers, followed by verapamil, droloxifen Z, tamoxifen, and droloxifen E in descending order. In addition to the modulators PSC 833 and dexniguldipine, droloxifen Z in particular is a candidate for future ex-vivo and in-vivo studies. The main advantage of Droloxifen Z could be the low rate of expected side effects. This fact allows the use of a high Drol Z dosage to achieve a relevant modulating effect in vivo and the use of this drug in combination with another modulator to achieve maximum efficacy with tolerable side effects.

UR - http://www.scopus.com/inward/record.url?scp=0032449860&partnerID=8YFLogxK

U2 - 10.3109/10428199809057619

AGAIN - 10.3109/10428199809057619

M3 - newspaper article

C2 - 9922050

AN - SCOPUS:0032449860

VL-31

SP-589

EP-597

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

SN-1042-8194

IS - 5-6

IS -

Nüssler V, Pelka-Fleisc R, Gieseler F, Hasmann M., Löser R., Gullis E. et al.In vitro efficacy of known P-glycoprotein modulators compared to droloxifene E and Z: studies on a human T-cell leukemia cell line and its resistant variants.leukemia and lymphoma. 1998;31(5-6):589-597. doi: 10.3109/10428199809057619