RAC FUNCTION MODULATES THE EFFECT ALKALINE GRADIENT ON CLEAR RENAL CELL CARCINOMA MORTALITY: ROLE OF ISOFORM 1 OF Na+/H+ EXCHANGER FUNCTION.

DI GIUSTO, GISELA; FORD, PAULA; CABRAL, BELEN ; BELTRAMONE, NATALIA; RIVAROLA, VALERIA; MECHALI, ANA; CAPURRO, CLAUDIA

Congreso; Reunión Anual SAFIS 2021; 2021

SAFIS

The association between proliferation and intracellular pH elicits the possibility that extracellular pH (pHe) may modify cell survival. Moreover, as tumor extracellular acidity is a hallmark of cancer, is probable that pHe affects differently cancer or normal cells. Our previous studies showed that cells derived from renal cell carcinoma (RCC) were more sensible to cell death after 72h exposition to 9.6 mM NaOH (mild alkalosis) than normal cells. Moreover, the combination of alkali plus inhibition of Na+/H+ exchanger isoform 1 (NHE1) improved normal tissue damage induced by alkali. The aim of this study was to investigate if this process were dependent on the Rho GTPases Rac1. We use three renal cell models: HK2, derived from normal human proximal epithelial cells, 786-O and Caki-1, both derived from human RCC. We exposed cells to Rac1 inhibitor IA116 alone or in combination with alkaline media or HOE 1uM, an NHE1 inhibitor. Then, we estimated cell survival by acrydin orange–ethidium bromide experiments. Our results show that after 72h inhibition of Rac induced cell dead in all cell lines. Alkaline-induced cell death was potentiated with Rac inhibition in HK2 and 786 O cells (% of alkaline-induced apoptosis: HK2 vehicle 25±5 vs 58±6, p