Diphenhydramine inhibits voltage-gated proton channel (Hv1) and induces acidification in leukemic Jurkat T cells. New evidence for the interpretation of antihistaminic drugs

ASUAJE AGUSTIN; MARTÍN PEDRO; ENRIQUE NICOLÁS; DÍAZ ZEGARRA LEANDRO; SMALDINI PAOLA; DOCENA GUILLERMO; MILESI VERÓNICA

CHANNELS

LANDES BIOSCIENCE

Lugar: Austin, Texas; Año: 2017

1933-6950

An established characteristic of neoplastic cells is their metabolic reprogramming, known as the Warburg effect, relying more on energetically less efficient pathways (such as glycolysis and pentose phosphate shunt) than in oxidative phosphorylation. This fact, results in an overproduction of acidic species that must be extruded in order to maintain intracellular homeostasis. We recently described, in leukemic cells, that blocking the proton currents mediated by then Hv1 ion channels derives in a marked intracellular acidification and apoptosis induction. Besides, the histamine H1-receptor antagonists were found to induce apoptosis in tumoral cells but the mechanism is still unclear. Here we show, in Jurkat T cells, how diphenhydramine inhibits Hv1 mediated currents inducing a drop in intracellular pH and cellular viability. This provides evidence of a new target structure responsible of the known pro-apoptotic action of antihistaminic drugs.