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Anti‐tumour/metastasis effects of the potassium‐sparing diuretic amiloride: An orally active anti‐cancer drug waiting for its call‐of‐duty?
Author(s) -
Matthews Hayden,
Ranson Marie,
Kelso Michael J.
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26156
Subject(s) - amiloride , metastasis , diuretic , cancer research , pharmacology , plasminogen activator , cancer , cancer cell , medicine , epithelial sodium channel , chemistry , sodium , organic chemistry
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.