Daunomycin accumulation in resistant tumor cells as a screening model for resistance modifying drugs: Role of protein binding

H. J. Broxterman, C. M. Kuiper, G. J. Schuurhuis, J. J M van der Hoeven, H. M. Pinedo, J. Lankelma

Research output: Contribution to journalArticle

Abstract

A potential screening system for drugs that modify anthracycline resistance was investigated. The effect of the calcium antagonistic agents verapamil, diltiazem, bepridil and Ro 11-2933/001 on daunorubicin (DNR) accumulation in the doxorubicin resistant cell line 2780AD was measured. For this purpose cells were suspended in medium with varying concentrations of bovine serum albumin (BSA) and in human plasma to establish the influence of protein binding on DNR accumulation. Increase of protein concentration did not affect DNR accumulation when no calcium antagonists were present but caused an increase in concentrations of calcium antagonists needed to promote DNR accumulation. It appeared that DNR accumulation in suspended cells correlated well with cytotoxicity assays, performed on cells growing in monolayer in 96-well microtiter plates, when accumulation was measured in medium with the same protein constitution as in growth medium (10% fetal calf serum). It is concluded that protein binding effects should be taken into account in the screening of compounds for the circumvention of multidrug resistance.

Original languageEnglish (US)
Pages (from-to)87-95
Number of pages9
JournalCancer Letters
Volume35
Issue number1
DOIs
StatePublished - 1987
Externally publishedYes

Fingerprint

Daunorubicin
Drug Resistance
Protein Binding
Neoplasms
Calcium
Bepridil
Preclinical Drug Evaluations
Diltiazem
Anthracyclines
Constitution and Bylaws
Multiple Drug Resistance
Bovine Serum Albumin
Verapamil
Doxorubicin
Proteins
Cell Line
Growth
Serum

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Broxterman, H. J., Kuiper, C. M., Schuurhuis, G. J., van der Hoeven, J. J. M., Pinedo, H. M., & Lankelma, J. (1987). Daunomycin accumulation in resistant tumor cells as a screening model for resistance modifying drugs: Role of protein binding. Cancer Letters, 35(1), 87-95. https://doi.org/10.1016/0304-3835(87)90060-7

Daunomycin accumulation in resistant tumor cells as a screening model for resistance modifying drugs : Role of protein binding. / Broxterman, H. J.; Kuiper, C. M.; Schuurhuis, G. J.; van der Hoeven, J. J M; Pinedo, H. M.; Lankelma, J.

In: Cancer Letters, Vol. 35, No. 1, 1987, p. 87-95.

Research output: Contribution to journalArticle

Broxterman, HJ, Kuiper, CM, Schuurhuis, GJ, van der Hoeven, JJM, Pinedo, HM & Lankelma, J 1987, 'Daunomycin accumulation in resistant tumor cells as a screening model for resistance modifying drugs: Role of protein binding', Cancer Letters, vol. 35, no. 1, pp. 87-95. https://doi.org/10.1016/0304-3835(87)90060-7
Broxterman, H. J. ; Kuiper, C. M. ; Schuurhuis, G. J. ; van der Hoeven, J. J M ; Pinedo, H. M. ; Lankelma, J. / Daunomycin accumulation in resistant tumor cells as a screening model for resistance modifying drugs : Role of protein binding. In: Cancer Letters. 1987 ; Vol. 35, No. 1. pp. 87-95.
@article{586365c07b9a40979c7136e54c00e8cd,
title = "Daunomycin accumulation in resistant tumor cells as a screening model for resistance modifying drugs: Role of protein binding",
abstract = "A potential screening system for drugs that modify anthracycline resistance was investigated. The effect of the calcium antagonistic agents verapamil, diltiazem, bepridil and Ro 11-2933/001 on daunorubicin (DNR) accumulation in the doxorubicin resistant cell line 2780AD was measured. For this purpose cells were suspended in medium with varying concentrations of bovine serum albumin (BSA) and in human plasma to establish the influence of protein binding on DNR accumulation. Increase of protein concentration did not affect DNR accumulation when no calcium antagonists were present but caused an increase in concentrations of calcium antagonists needed to promote DNR accumulation. It appeared that DNR accumulation in suspended cells correlated well with cytotoxicity assays, performed on cells growing in monolayer in 96-well microtiter plates, when accumulation was measured in medium with the same protein constitution as in growth medium (10{\%} fetal calf serum). It is concluded that protein binding effects should be taken into account in the screening of compounds for the circumvention of multidrug resistance.",
author = "Broxterman, {H. J.} and Kuiper, {C. M.} and Schuurhuis, {G. J.} and {van der Hoeven}, {J. J M} and Pinedo, {H. M.} and J. Lankelma",
year = "1987",
doi = "10.1016/0304-3835(87)90060-7",
language = "English (US)",
volume = "35",
pages = "87--95",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Daunomycin accumulation in resistant tumor cells as a screening model for resistance modifying drugs

T2 - Role of protein binding

AU - Broxterman, H. J.

AU - Kuiper, C. M.

AU - Schuurhuis, G. J.

AU - van der Hoeven, J. J M

AU - Pinedo, H. M.

AU - Lankelma, J.

PY - 1987

Y1 - 1987

N2 - A potential screening system for drugs that modify anthracycline resistance was investigated. The effect of the calcium antagonistic agents verapamil, diltiazem, bepridil and Ro 11-2933/001 on daunorubicin (DNR) accumulation in the doxorubicin resistant cell line 2780AD was measured. For this purpose cells were suspended in medium with varying concentrations of bovine serum albumin (BSA) and in human plasma to establish the influence of protein binding on DNR accumulation. Increase of protein concentration did not affect DNR accumulation when no calcium antagonists were present but caused an increase in concentrations of calcium antagonists needed to promote DNR accumulation. It appeared that DNR accumulation in suspended cells correlated well with cytotoxicity assays, performed on cells growing in monolayer in 96-well microtiter plates, when accumulation was measured in medium with the same protein constitution as in growth medium (10% fetal calf serum). It is concluded that protein binding effects should be taken into account in the screening of compounds for the circumvention of multidrug resistance.

AB - A potential screening system for drugs that modify anthracycline resistance was investigated. The effect of the calcium antagonistic agents verapamil, diltiazem, bepridil and Ro 11-2933/001 on daunorubicin (DNR) accumulation in the doxorubicin resistant cell line 2780AD was measured. For this purpose cells were suspended in medium with varying concentrations of bovine serum albumin (BSA) and in human plasma to establish the influence of protein binding on DNR accumulation. Increase of protein concentration did not affect DNR accumulation when no calcium antagonists were present but caused an increase in concentrations of calcium antagonists needed to promote DNR accumulation. It appeared that DNR accumulation in suspended cells correlated well with cytotoxicity assays, performed on cells growing in monolayer in 96-well microtiter plates, when accumulation was measured in medium with the same protein constitution as in growth medium (10% fetal calf serum). It is concluded that protein binding effects should be taken into account in the screening of compounds for the circumvention of multidrug resistance.

UR - http://www.scopus.com/inward/record.url?scp=0023091199&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023091199&partnerID=8YFLogxK

U2 - 10.1016/0304-3835(87)90060-7

DO - 10.1016/0304-3835(87)90060-7

M3 - Article

C2 - 3471315

AN - SCOPUS:0023091199

VL - 35

SP - 87

EP - 95

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 1

ER -