Different effects of metabolic inhibitors and cyclosporin A on daunorubicin transport in leukemia cells from patients with AML

The objective of this study was to determine the role of transport proteins in daunorubicin (Dnr) accumulation and efflux in leukemia cells from 36 patients with acute myeloid leukemia (AML). Mononuclear cells were isolated and incubated with 1 μM Dnr with/without addition of 3 μM cyclosporin A (CyA...

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Bibliographic Details
Published in:Leukemia research 2003-02, Vol.27 (2), p.183-191
Main Authors: Knaust, Eva, Porwit-MacDonald, Anna, Gruber, Astrid, Xu, Dawei, Peterson, Curt
Format: Article
Language:English
Subjects:
Accumulation and efflux
Acute Disease
Adult
Aged
Aged, 80 and over
Antineoplastic agents
ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology
Biological and medical sciences
Carrier Proteins - genetics
Carrier Proteins - physiology
Cyclosporin A
Cyclosporine - pharmacology
Daunorubicin
Daunorubicin - pharmacokinetics
Enzyme Inhibitors - pharmacology
Female
General aspects
Human AML cells
Humans
Iodoacetates - pharmacology
Leukemia, Myeloid - drug therapy
Leukemia, Myeloid - metabolism
Leukemia, Myeloid - pathology
Male
Medical sciences
MEDICIN
Medicin och hälsovetenskap
MEDICINE
Metabolic inhibitors
Middle Aged
Multidrug Resistance-Associated Proteins - genetics
Multidrug Resistance-Associated Proteins - physiology
Neoplasm Proteins - genetics
Neoplasm Proteins - physiology
Pharmacology. Drug treatments
RNA, Messenger - analysis
Sodium Azide - pharmacology
Vault Ribonucleoprotein Particles - genetics
Vault Ribonucleoprotein Particles - physiology
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Summary:The objective of this study was to determine the role of transport proteins in daunorubicin (Dnr) accumulation and efflux in leukemia cells from 36 patients with acute myeloid leukemia (AML). Mononuclear cells were isolated and incubated with 1 μM Dnr with/without addition of 3 μM cyclosporin A (CyA) or metabolic inhibitors (MI). Cellular Dnr concentration in leukemia blast cells was measured with flow cytometry. After washing and reincubation of the cells in drug-free medium, Dnr efflux was followed with/without addition of CyA or MI. Levels of mRNA expression for mdr1, multidrug resistance associated protein (mrp) and lung resistance protein (lrp) were determined with reverse transcriptase-polymerase chain reaction (RT-PCR). MI enhanced cellular Dnr accumulation to a higher extent than CyA whereas CyA reduced Dnr efflux more efficiently than MI ( P
ISSN:0145-2126
1873-5835
1873-5835
DOI:10.1016/S0145-2126(02)00093-0