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

Publication date: Available online 18 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Jihu Dong, Francisco Aulestia, Suzana Assad Kahn, Maria Zeniou, Luiz Gustavo Dubois, Elias A. El-Habr, François Daubeuf, Nassera Tounsi, Samuel H. Cheshier, Nelly Frossard, Marie-Pierre Junier, Hervé Chneiweiss, Isabelle Néant, Marc Moreau, Catherine Leclerc, Jacques Haiech, Marie-Claude Kilhoffer
Glioblastoma is the most common malignant brain tumor. The heterogeneity at the cellular level, metabolic specificities and plasticity of the cancer cells are a challenge for glioblastoma treatment. Identification of cancer cells endowed with stem properties and able to propagate the tumor in animal xenografts has opened a new paradigm in cancer therapy. Thus, to increase efficacy and avoid tumor recurrence, therapies need to target not only the differentiated cells of the tumor mass, but also the cancer stem-like cells. These therapies need to be effective on cells present in the hypoxic, slightly acidic microenvironment found within tumors. Such a microenvironment is known to favor more aggressive undifferentiated phenotypes and a slow-growing “quiescent state” that preserves the cells from chemotherapeutic agents, which mostly target proliferating cells. Based on these considerations, we performed a differential screening of the Prestwick Chemical Library of approved drugs on both proliferating and quiescent glioblastoma stem-like cells and 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. Our work further suggests that bisacodyl acts through inhibition of Ca²⁺ release from the InsP3 receptors.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2jOhpef
via IFTTT