Apoptosis and resistance to daunorubicin in human leukemic cells

Autoren

T Efferth
U Fabry
R Osieka

DOI

10.1038/sj.leu.2400669

eISSN

1476-5551

ISSN

0887-6924

Ausgabe der Veröffentlichung

7

Zeitschrift

Leukemia

Sprache

en

Paginierung

1180 - 1186

Datum der Veröffentlichung

1997

Status

Published

Herausgeber

Springer Science and Business Media LLC

Herausgeber URL

http://dx.doi.org/10.1038/sj.leu.2400669

Datum der Datenerfassung

2022

Titel

Apoptosis and resistance to daunorubicin in human leukemic cells

Ausgabe der Zeitschrift

11

Data source: Crossref

Abstract

We compared test methods based on specific mechanisms of daunorubicin (DNR) resistance to more global procedures. Assessment of P-glycoprotein (P-gp) expression and function by means of immunocytochemistry, DNR accumulation, and modulation of resistance and accumulation by the P-gp inhibitor cyclosporin A (CsA) were selected as parameters for multidrug resistance (MDR). On the other hand, we used the MTT assay and measured apoptosis and proliferative activity (S- and G2M-phases of the cell cycle) by flow cytometry. Validation of test methods was achieved for four leukemic cell lines (HL-60, KG-1a, K562/WT, K562/ADM). This battery of tests was then applied to mononuclear cells (MNC) from 18 leukemic patients. Low proficiency of MNC to undergo apoptosis and low proliferative activity rather than P-gp-mediated MDR correlated with DNR resistance as measured by the MTT assay. Bell-shaped dose-response curves for apoptosis, however, which reflect a switch from the apoptotic to the necrotic death mode with increasing cellular damage tend to limit practicability in clinical testing, because appropriate dose range and time points need to be explored. Thus, measurement of apoptosis by flow cytometry may be less convenient than the MTT assay for determination of chemosensitivity, if clinical samples with unknown patterns of responsiveness are to be tested. Spontaneous apoptosis in untreated MNC following 24 h incubation in vitro correlated significantly with DNR sensitivity in the MTT assay. A lack of essential viability factors (eg growth factors or cytokines) in vitro which are known to prevent apoptosis may contribute to DNR sensitivity.

Addresses

Medizinische Klinik IV, der RWTH Aachen, Germany.

Autoren

T Efferth
T Efferth
U Fabry
R Osieka

DOI

10.1038/sj.leu.2400669

eISSN

1476-5551

Externe Identifier

PubMed Identifier: 9205009

Open access

false

ISSN

0887-6924

Ausgabe der Veröffentlichung

7

Zeitschrift

Leukemia

Schlüsselwörter

Tumor Cells, Cultured
Humans
Leukemia
Tetrazolium Salts
Thiazoles
Daunorubicin
Antibiotics, Antineoplastic
Apoptosis
Drug Resistance

Sprache

eng

Medium

Print

Paginierung

1180 - 1186

Datum der Veröffentlichung

1997

Status

Published

Datum der Datenerfassung

1997

Titel

Apoptosis and resistance to daunorubicin in human leukemic cells.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

11

Data source: Europe PubMed Central

Abstract

We compared test methods based on specific mechanisms of daunorubicin (DNR) resistance to more global procedures. Assessment of P-glycoprotein (P-gp) expression and function by means of immunocytochemistry, DNR accumulation, and modulation of resistance and accumulation by the P-gp inhibitor cyclosporin A (CsA) were selected as parameters for multidrug resistance (MDR). On the other hand, we used the MTT assay and measured apoptosis and proliferative activity (S- and G2M-phases of the cell cycle) by flow cytometry. Validation of test methods was achieved for four leukemic cell lines (HL-60, KG-1a, K562/WT, K562/ADM). This battery of tests was then applied to mononuclear cells (MNC) from 18 leukemic patients. Low proficiency of MNC to undergo apoptosis and low proliferative activity rather than P-gp-mediated MDR correlated with DNR resistance as measured by the MTT assay. Bell-shaped dose-response curves for apoptosis, however, which reflect a switch from the apoptotic to the necrotic death mode with increasing cellular damage tend to limit practicability in clinical testing, because appropriate dose range and time points need to be explored. Thus, measurement of apoptosis by flow cytometry may be less convenient than the MTT assay for determination of chemosensitivity, if clinical samples with unknown patterns of responsiveness are to be tested. Spontaneous apoptosis in untreated MNC following 24 h incubation in vitro correlated significantly with DNR sensitivity in the MTT assay. A lack of essential viability factors (eg growth factors or cytokines) in vitro which are known to prevent apoptosis may contribute to DNR sensitivity.

Autoren

T Efferth
U Fabry
R Osieka

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/9205009

DOI

10.1038/sj.leu.2400669

ISSN

0887-6924

Ausgabe der Veröffentlichung

7

Zeitschrift

Leukemia

Schlüsselwörter

Antibiotics, Antineoplastic
Apoptosis
Daunorubicin
Drug Resistance
Humans
Leukemia
Tetrazolium Salts
Thiazoles
Tumor Cells, Cultured

Sprache

eng

Country

England

Paginierung

1180 - 1186

Datum der Veröffentlichung

1997

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

1997

Titel

Apoptosis and resistance to daunorubicin in human leukemic cells.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

11

Data source: PubMed

Apoptosis and resistance to daunorubicin in human leukemic cells

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