Cancer cells are characterized by a peculiar pH condition, being the
extracellular compartment acidic and the intracellular one neutral or basic, i.e. the
opposite of what happens in normal cells. The reversal of the pH contributes to
cancer cell proliferation and drug resistance. Among the different enzymes regulating
pH gradient, proton transporters Na+/H+ exchangers (NHEs) are considered
as suitable targets for drugs that ultimately counteract cancer cell survival. This
review will describe the properties of NHEs, focusing on the prototype NHE1 and
on the effect of its inhibition on cancer cell metabolism.
Keywords: Amiloride, cancer cells, cariporide, NHEs, intracellular pH (pHi), tumor microenvironment, Warburg effect.
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