Na<sup>+</sup>/K<sup>+</sup>-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation
Maintenance of Na<sup>+</sup> and K<sup>+</sup> gradients across the cell plasma membrane is an essential process for mammalian cell survival. An enzyme responsible for this process, sodium-potassium ATPase (NKA), has been currently extensively studied as a potential anticanc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/7/1905 |
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| author | Jiří Bejček Vojtěch Spiwok Eva Kmoníčková Silvie Rimpelová |
| author_facet | Jiří Bejček Vojtěch Spiwok Eva Kmoníčková Silvie Rimpelová |
| author_sort | Jiří Bejček |
| collection | DOAJ |
| description | Maintenance of Na<sup>+</sup> and K<sup>+</sup> gradients across the cell plasma membrane is an essential process for mammalian cell survival. An enzyme responsible for this process, sodium-potassium ATPase (NKA), has been currently extensively studied as a potential anticancer target, especially in lung cancer and glioblastoma. To date, many NKA inhibitors, mainly of natural origin from the family of cardiac steroids (CSs), have been reported and extensively studied. Interestingly, upon CS binding to NKA at nontoxic doses, the role of NKA as a receptor is activated and intracellular signaling is triggered, upon which cancer cell death occurs, which lies in the expression of different NKA isoforms than in healthy cells. Two major CSs, digoxin and digitoxin, originally used for the treatment of cardiac arrhythmias, are also being tested for another indication—cancer. Such drug repositioning has a big advantage in smoother approval processes. Besides this, novel CS derivatives with improved performance are being developed and evaluated in combination therapy. This article deals with the NKA structure, mechanism of action, activity modulation, and its most important inhibitors, some of which could serve not only as a powerful tool to combat cancer, but also help to decipher the so-far poorly understood NKA regulation. |
| first_indexed | 2024-03-10T12:48:57Z |
| format | Article |
| id | doaj.art-00885bd58ab145918cee7ccf1591c6a2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T12:48:57Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-00885bd58ab145918cee7ccf1591c6a22023-11-21T13:09:52ZengMDPI AGMolecules1420-30492021-03-01267190510.3390/molecules26071905Na<sup>+</sup>/K<sup>+</sup>-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity ModulationJiří Bejček0Vojtěch Spiwok1Eva Kmoníčková2Silvie Rimpelová3Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 3, 166 28 Prague 6, Czech RepublicDepartment of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 3, 166 28 Prague 6, Czech RepublicDepartment of Pharmacology, Second Faculty of Medicine, Charles University, Plzeňská 311, 150 00 Prague, Czech RepublicDepartment of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 3, 166 28 Prague 6, Czech RepublicMaintenance of Na<sup>+</sup> and K<sup>+</sup> gradients across the cell plasma membrane is an essential process for mammalian cell survival. An enzyme responsible for this process, sodium-potassium ATPase (NKA), has been currently extensively studied as a potential anticancer target, especially in lung cancer and glioblastoma. To date, many NKA inhibitors, mainly of natural origin from the family of cardiac steroids (CSs), have been reported and extensively studied. Interestingly, upon CS binding to NKA at nontoxic doses, the role of NKA as a receptor is activated and intracellular signaling is triggered, upon which cancer cell death occurs, which lies in the expression of different NKA isoforms than in healthy cells. Two major CSs, digoxin and digitoxin, originally used for the treatment of cardiac arrhythmias, are also being tested for another indication—cancer. Such drug repositioning has a big advantage in smoother approval processes. Besides this, novel CS derivatives with improved performance are being developed and evaluated in combination therapy. This article deals with the NKA structure, mechanism of action, activity modulation, and its most important inhibitors, some of which could serve not only as a powerful tool to combat cancer, but also help to decipher the so-far poorly understood NKA regulation.https://www.mdpi.com/1420-3049/26/7/1905anticancer activitycardiac glycosidescombination therapydigoxindigitoxindigitoxigenin |
| spellingShingle | Jiří Bejček Vojtěch Spiwok Eva Kmoníčková Silvie Rimpelová Na<sup>+</sup>/K<sup>+</sup>-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation Molecules anticancer activity cardiac glycosides combination therapy digoxin digitoxin digitoxigenin |
| title | Na<sup>+</sup>/K<sup>+</sup>-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation |
| title_full | Na<sup>+</sup>/K<sup>+</sup>-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation |
| title_fullStr | Na<sup>+</sup>/K<sup>+</sup>-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation |
| title_full_unstemmed | Na<sup>+</sup>/K<sup>+</sup>-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation |
| title_short | Na<sup>+</sup>/K<sup>+</sup>-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation |
| title_sort | na sup sup k sup sup atpase revisited on its mechanism of action role in cancer and activity modulation |
| topic | anticancer activity cardiac glycosides combination therapy digoxin digitoxin digitoxigenin |
| url | https://www.mdpi.com/1420-3049/26/7/1905 |
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