Pyrazine ring-based Na⁺/H⁺ exchanger (NHE) inhibitors potently inhibit cancer cell growth in 3D culture, independent of NHE1.

ABSTRACT: The Na⁺/H⁺ exchanger-1 (NHE1) supports tumour growth, making NHE1 inhibitors of interest in anticancer therapy, yet their molecular effects are incompletely characterized. Here, we demonstrate that widely used pyrazinoylguanidine-type NHE1 inhibitors potently inhibit growth and survival of cancer cell spheroids, in a manner unrelated to NHE1 inhibition. Cancer and non-cancer cells were grown as 3-dimensional (3D) spheroids and treated with pyrazinoylguanidine-type (amiloride, 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), 5-(N,N-dimethyl)-amiloride (DMA), and 5-(N,N-hexamethylene)-amiloride (HMA)) or benzoylguanidine-type (eniporide, cariporide) NHE1 inhibitors for 2-7 days, followed by analyses of viability, compound accumulation, and stress- and death-associated signalli

SUBMITTER: Rolver MG 

PROVIDER: S-EPMC7118118 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature