IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effect of alkaline gradient on clear renal cell carcinoma mortality: role of isoform 1 of Na+/H+ exchanger function
Autor/es:
MAZZOCCHI M; BELTRAMONE N; RIVAROLA V; DI GIUSTO G; FORD P; PIZZONI A; CAPURRO C
Lugar:
Rosario
Reunión:
Congreso; Reunión Anual de la Sociedad Argentina de Fisiología 2019; 2019
Institución organizadora:
Sociedad Argentina de Fisiología
Resumen:
The association between cell death and intracellular pH elicits the possibility that extracellular pH (pHe) may modify cell survival. Moreover, as tumor extracellular acidity is a hallmark of cancers, 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 24h alkalosis than normal cells. The aim of this study was to investigate further the best alkaline condition to kill cancer cells without affecting normal ones. 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 media with different alkaline pHe during 48 to 96h. Then, we estimated cell survival by acrydin orange?ethidium bromide experiments. Our results show that normal HK2 cells could survive up to 72h in very mild alkaline conditions (4.8mM NaOH, + 0.05 pH units) without being affected (94±16 % of living cells respect to control, n=6). At the same conditions, both RCC derived cell lines had significant fewer % of living cells respect to control (64±5 % for 786-O and 72±7 % for Caki-1 cells, both with n=6). With 72h exposition to 9.6 mM NaOH (+ 0.1 pH units) the percentage of living RCC cells respect to control became minimal (23±8 % for 786-O and 16±5 % for Caki-1 cells, both with n=6). However, at this condition HK2 cells were also affected (28±5 % of living cells respect to control, n=6). NHE1 isoform of Na+/H+ exchanger favors apoptotic process in some experimental models. Then, we inhibited the transporter during the 72h exposition to 9.6 mM NaOH. NHE1 inhibition partially reverted the effects of alkalosis only in normal HK2 cells (% of living cells respect to control: +NHE1 28±5 vs ?NHE1 54±6, p