Effect of verapamil and other agents on the distribution of anthracyclines and on reversal of drug resistance

We studied the intracellular distribution of drugs within anthracycline-sensitive and -resistant cells by computer-assisted digitized video fluorescence microscopy. We found that the antitumor antibiotic, daunorubicin, distributes differently in anthracycline-sensitive and -resistant human leukemia...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1987-03, Vol.47 (5), p.1421-1425
Main Authors: HINDENBURG, A. A, BAKER, M. A, GLEYZER, E, STEWART, V. J, CASE, N, TAUB, R. N
Format: Article
Language:English
Subjects:
Antibiotics, Antineoplastic - metabolism
Antineoplastic agents
Biological and medical sciences
Cell Line
Daunorubicin - metabolism
Doxorubicin - metabolism
Drug Resistance
General aspects
Humans
Leukemia, Myeloid, Acute - metabolism
Medical sciences
Naphthacenes - metabolism
Naphthacenes - pharmacology
Pharmacology. Drug treatments
Solubility
Verapamil - pharmacology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We studied the intracellular distribution of drugs within anthracycline-sensitive and -resistant cells by computer-assisted digitized video fluorescence microscopy. We found that the antitumor antibiotic, daunorubicin, distributes differently in anthracycline-sensitive and -resistant human leukemia cells (HL-60). Verapamil and other agents known to circumvent resistance in pleiotropic drug-resistant cell lines were able to change the pattern of distribution of daunorubicin in the anthracycline-resistant HL-60 cells back to the distribution found in anthracycline-sensitive HL-60 cells. To investigate the biochemical basis for this effect, we studied the distribution of daunorubicin and doxorubicin in a hydrophobic/hydrophilic (membrane/cytoplasmic) environment using the two-compartment cell-free system of Folch. Our results demonstrate that various unrelated drugs known to overcome resistance will also change the distribution of the anthracyclines in the hydrophobic/hydrophilic compartments. Our data allow the hypothesis that various unrelated agents known to circumvent resistance may act by altering the hydrophobic/hydrophilic solubility of anthracyclines in the resistant cell.
ISSN:0008-5472
1538-7445