Cytotoxicity of cardiotonic steroids in sensitive and multidrug-resistant leukemia cells and the link with Na+/K+-ATPase

Autoren

Maen Zeino
Ruth Brenk
Lisa Gruber
Martin Zehl
Ernst Urban
Brigitte Kopp
Thomas Efferth

DOI

10.1016/j.jsbmb.2015.03.008

ISSN

0960-0760

Zeitschrift

The Journal of Steroid Biochemistry and Molecular Biology

Sprache

en

Paginierung

97 - 111

Datum der Veröffentlichung

2015

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.jsbmb.2015.03.008

Datum der Datenerfassung

2022

Titel

Cytotoxicity of cardiotonic steroids in sensitive and multidrug-resistant leukemia cells and the link with Na+/K+-ATPase

Ausgabe der Zeitschrift

150

Data source: Crossref

Abstract

Cardiotonic steroids have long been in clinical use for treatment of heart failure and are now emerging as promising agents in various diseases, especially cancer. Their main target is Na(+)/K(+)-ATPase, a membrane protein involved in cellular ion homeostasis. Na(+)/K(+)-ATPase has been implicated in cancer biology by affecting several cellular events and signaling pathways in both sensitive and drug-resistant cancer cells. Hence, we investigated the cytotoxic activities of 66 cardiotonic steroids and cardiotonic steroid derivatives in sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. Data were then subjected to quantitative structure-activity relationship analysis (QSAR) and molecular docking into Na(+)/K(+)-ATPase, which both indicated a possible differential expression of the pump in the mentioned cell lines. This finding was confirmed by western blotting, intracellular potassium labeling and next generation sequencing which showed that Na(+)/K(+)-ATPase was less expressed in multidrug-resistant than in sensitive cells.

Addresses

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.

Autoren

Maen Zeino
Ruth Brenk
Lisa Gruber
Martin Zehl
Ernst Urban
Brigitte Kopp
Thomas Efferth
Thomas Efferth

DOI

10.1016/j.jsbmb.2015.03.008

eISSN

1879-1220

Externe Identifier

PubMed Identifier: 25797029

Open access

false

ISSN

0960-0760

Zeitschrift

The Journal of steroid biochemistry and molecular biology

Schlüsselwörter

Leukocytes, Mononuclear
Cell Line, Tumor
Humans
Verapamil
Doxorubicin
Bufanolides
Digoxin
Cardiac Glycosides
Antineoplastic Agents
Drug Resistance, Multiple
Signal Transduction
Cell Survival
Gene Expression
Quantitative Structure-Activity Relationship
Drug Resistance, Neoplasm
Sodium-Potassium-Exchanging ATPase
Primary Cell Culture
Molecular Docking Simulation

Sprache

eng

Medium

Print-Electronic

Online publication date

2015

Paginierung

97 - 111

Datum der Veröffentlichung

2015

Status

Published

Datum der Datenerfassung

2015

Titel

Cytotoxicity of cardiotonic steroids in sensitive and multidrug-resistant leukemia cells and the link with Na(+)/K(+)-ATPase.

Sub types

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

Ausgabe der Zeitschrift

150

Data source: Europe PubMed Central

Abstract

Cardiotonic steroids have long been in clinical use for treatment of heart failure and are now emerging as promising agents in various diseases, especially cancer. Their main target is Na(+)/K(+)-ATPase, a membrane protein involved in cellular ion homeostasis. Na(+)/K(+)-ATPase has been implicated in cancer biology by affecting several cellular events and signaling pathways in both sensitive and drug-resistant cancer cells. Hence, we investigated the cytotoxic activities of 66 cardiotonic steroids and cardiotonic steroid derivatives in sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. Data were then subjected to quantitative structure-activity relationship analysis (QSAR) and molecular docking into Na(+)/K(+)-ATPase, which both indicated a possible differential expression of the pump in the mentioned cell lines. This finding was confirmed by western blotting, intracellular potassium labeling and next generation sequencing which showed that Na(+)/K(+)-ATPase was less expressed in multidrug-resistant than in sensitive cells.

Date of acceptance

2015

Autoren

Maen Zeino
Ruth Brenk
Lisa Gruber
Martin Zehl
Ernst Urban
Brigitte Kopp
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/25797029

DOI

10.1016/j.jsbmb.2015.03.008

eISSN

1879-1220

Zeitschrift

J Steroid Biochem Mol Biol

Schlüsselwörter

Cardiotonic steroids
Multidrug resistance
Na(+)/K(+)-ATPase signalosome
Next generation sequencing
Antineoplastic Agents
Bufanolides
Cardiac Glycosides
Cell Line, Tumor
Cell Survival
Digoxin
Doxorubicin
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Gene Expression
Humans
Leukocytes, Mononuclear
Molecular Docking Simulation
Primary Cell Culture
Quantitative Structure-Activity Relationship
Signal Transduction
Sodium-Potassium-Exchanging ATPase
Verapamil

Sprache

eng

Country

England

Paginierung

97 - 111

PII

S0960-0760(15)00093-X

Datum der Veröffentlichung

2015

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2015

Titel

Cytotoxicity of cardiotonic steroids in sensitive and multidrug-resistant leukemia cells and the link with Na(+)/K(+)-ATPase.

Sub types

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

Ausgabe der Zeitschrift

150

Data source: PubMed

Cytotoxicity of cardiotonic steroids in sensitive and multidrug-resistant leukemia cells and the link with Na+/K+-ATPase

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