engleski

Tumour growth could be markedly suppressed by inhibition of intracellular pH regulating mechanisms

Measurements of extracellular pH (pHe) in normal and tumour tissues have shown that microenvironment in tumour tissue is generally more acidic than in normal tissues, while the intracellular pH (pHi) do not differ. Main mechanisms, responsible for tumour acidity, involve the production of lactic acid and consequent hydrolysis of ATP in hypoxic regions of tumours. To survive, normal and, especially, tumour cells have to develop and actively control mechanisms for pHi regulation. Two main pHi regulating mechanisms are Na+/H+ antiport and Na+-dependent HCO3-/Cl- exchanger. It is possible to inhibit Na+/H+ antiport by amiloride and its derivatives, and Na+-dependent HCO3-/Cl- exchanger by stilbene derivatives. The survival of tumour and normal cells depends on ability of these exchangers to maintain pHi at physiological level while the pHe is low. Their activity is particulary important for cytoplasmic alkalinisation which triggers the mitogenesis and proliferation of cells. The results of our experiments in vitro and in vivo, as well as results of others investigations, have demonstrated the antitumour effect induced by inhibition of Na+/H+ antiport and Na+-dependent HCO3-/Cl- exchanger. The possibility of a new approach to antitumour therapy based on inhibition of ion exchangers that regulate pHi should be considered in future.

tumour; intracellular and extracellular pH; ion exchangers

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