Na+/K+ ATP酶抑制剂在肿瘤中的作用

Title:Na⁺/K⁺ ATPase Inhibitors in Cancer

Volume: 15 Issue: 10

Author(s): Konstantinos Alevizopoulos, Theodora Calogeropoulou, Florian Lang and Christos Stournaras

Affiliation:

关键词: Bufadienolides，蟾蜍灵，癌症治疗，强心苷，强心类固醇，地高辛，istaroxime，Na +/ K + ATP酶，钠钾ATP酶，Na +/ K + ATP酶甾体抑制剂

摘要: Sodium potassium pump (Na⁺/K⁺ ATPase) is a transmembrane protein complex found in all higher eukaryotes acting as a key energy-consuming pump maintaining ionic and osmotic balance in cells. Recently recognized as an important transducer and/or integrator of various signals as well as a protein-protein interaction scaffold forming receptor complexes with signaling properties, the most prominent pharmacological role of Na⁺/K⁺ ATPase inhibitors is the increase of myocardial contractility in pathologic conditions such as congestive heart failure. Consequently, modulators of Na⁺/K⁺ ATPase such as digoxin have been approved by regulatory authorities and are widely used in the treatment of cardiac failure since 1975. Initiating from early observations of reduction of cancer incidence in cardiac patients taking digoxin, recent epidemiological and other studies have consolidated the anti-cancer potential of Na⁺/K⁺ ATPase inhibitors in indications such as prostate, breast, lung cancer or leukemia. More importantly, a new series of pharmacologically optimized Na⁺/K⁺ ATPase inhibitors has recently shown strong anti-cancer activities in multiple preclinical assays and have reached early clinical trials. Altogether, these results suggest that Na⁺/K⁺ ATPase is an emerging cancer target that merits further investigation. In this review, we summarize key functional properties of the enzyme that are highly relevant for cancer cell selectivity, review the most prominent chemical classes of Na⁺/K⁺ ATPase inhibitors and analyze their downstream effectors. Moreover, we discuss overall development prospects of these candidate drugs on their way to becoming new effective treatments of cancer in patients.

Cite this article as:

Alevizopoulos Konstantinos, Calogeropoulou Theodora, Lang Florian and Stournaras Christos, Na⁺/K⁺ ATPase Inhibitors in Cancer, Current Drug Targets 2014; 15 (10) . https://dx.doi.org/10.2174/1389450115666140908125025