WNK1 kinase and its partners Akt, SGK1 and NBC-family Na⁺/HCO3^- cotransporters are potential therapeutic targets for glioblastoma stem-like cells linked to Bisacodyl signaling.

ABSTRACT: Glioblastoma is a highly heterogeneous brain tumor. The presence of cancer cells with stem-like and tumor initiation/propagation properties contributes to poor prognosis. Glioblastoma cancer stem-like cells (GSC) reside in hypoxic and acidic niches favoring cell quiescence and drug resistance. A high throughput screening recently identified the laxative Bisacodyl as a cytotoxic compound targeting quiescent GSC placed in acidic microenvironments. Bisacodyl activity requires its hydrolysis into DDPM, its pharmacologically active derivative. Bisacodyl was further shown to induce tumor shrinking and increase survival in in vivo glioblastoma models. Here we explored the cellular mechanism underlying Bisacodyl cytotoxic effects using quiescent GSC in an acidic microenvironment and GSC-der

SUBMITTER: Chen W 

PROVIDER: S-EPMC6007472 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature