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Bisacodyl and its cytotoxic activity on human glioblastoma stem-like cells. Implication of inositol 1,4,5-triphosphate receptor dependent calcium signaling.

par Eric AGIUS - publié le

To avoid glioblastoma tumor recurrence, therapies need to target not only the differentiated cells of the tumor mass, but also the cancer stem-like cells (CSLCs) present in the hypoxic, slightly acidic microenvironment found within tumors. This microenvironment is known to favor a quiescent state that preserves the CSLCs from chemotherapeutic agents, which mostly target proliferating cells. Based on these considerations, a differential screening of the Prestwick Chemical Library identified bisacodyl as a cytotoxic agent with selectivity for quiescent glioblastoma stem-like cells. In the present study we further characterize bisacodyl activity and show its efficacy in vitro on clonal macro-tumorospheres, as well as in vivo in glioblastoma mouse models and unveil the implication of Ca2+ signaling in the effect of the molecule through the inhibition of Ca2+ release from the InsP3 receptors.