Anti‐tumour/metastasis effects of the potassium‐sparing diuretic amiloride: An orally active anti‐cancer drug waiting for its call‐of‐duty?

Amiloride.HCl is clinically used as an oral potassium‐sparing diuretic, but multiple studies in biochemical, cellular and animal models have shown that the drug also possesses anti‐tumour and anti‐metastasis activities. The additional effects appear to arise through inhibition of two discrete target...

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Bibliographic Details
Published in:International journal of cancer 2011-11, Vol.129 (9), p.2051-2061
Main Authors: Matthews, Hayden, Ranson, Marie, Kelso, Michael J.
Format: Article
Language:English
Subjects:
Administration, Oral
amiloride
Amiloride - administration & dosage
Amiloride - pharmacology
Amiloride - therapeutic use
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
anti‐metastasis drug
Biological and medical sciences
chemotherapy
Disease Models, Animal
Humans
Medical sciences
metastasis
Neoplasm Metastasis - drug therapy
Neoplasms - drug therapy
NHE
plasminogen activation system
Sodium Channel Blockers - administration & dosage
Sodium Channel Blockers - pharmacology
Sodium Channel Blockers - therapeutic use
Sodium-Hydrogen Exchangers - antagonists & inhibitors
Tumors
uPA
Urokinase-Type Plasminogen Activator - antagonists & inhibitors
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Summary:Amiloride.HCl is clinically used as an oral potassium‐sparing diuretic, but multiple studies in biochemical, cellular and animal models have shown that the drug also possesses anti‐tumour and anti‐metastasis activities. The additional effects appear to arise through inhibition of two discrete targets: (i) the sodium–hydrogen exchanger 1 (NHE1), a membrane protein responsible for the characteristically low extracellular pH of tumours and (ii) the urokinase‐type plasminogen activator (uPA), a serine protease mediator of cell migration, invasion and metastasis and well‐known marker of poor prognosis in cancer. This mini‐review summarises for the first time the reported anti‐tumour/metastasis effects of amiloride in experimental models, discusses the putative molecular mechanisms responsible for these effects and concludes by commenting on the pros and cons of trialling amiloride or one of its structural analogues as potential new anti‐tumour/metastasis drugs.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.26156