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

The Journal of Steroid Biochemistry and Molecular Biology
Maen ZeinoThomas Efferth

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.

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Citations

Apr 9, 2016·Journal of Ethnopharmacology·Mohamed E M SaeedThomas Efferth
Aug 25, 2016·Biochemical Pharmacology·Marc DiederichClaudia Cerella
Apr 22, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cassiano Felippe Gonçalves-de-AlbuquerquePatrícia Burth
Jun 15, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xiaoyu Cui, Zijian Xie
Jul 7, 2020·Molecular Diversity·Salvador Enrique Meneses-SagreroRamón Enrique Robles-Zepeda
Mar 17, 2018·Frontiers in Pharmacology·Naira F Z SchneiderMarc Diederich
Mar 5, 2021·Journal of the Egyptian National Cancer Institute·Mariah FarrugiaPierre Schembri Wismayer
Jan 29, 2020·Phytochemistry·Tomoki IguchiYoshihiro Mimaki
Aug 8, 2020·European Journal of Pharmacology·Li-Juan DengDong-Mei Zhang

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