Fiche publication
Date publication
janvier 2017
Journal
Biochimica et biophysica acta
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HAIECH Jacques
,
Dr ZENIOU-MEYER Maria
,
Dr TOUNSI Nassera
Tous les auteurs :
Dong J, Aulestia FJ, Assad Kahn S, Zeniou M, Dubois LG, El-Habr EA, Daubeuf F, Tounsi N, Cheshier SH, Frossard N, Junier MP, Chneiweiss H, Néant I, Moreau M, Leclerc C, Haiech J, Kilhoffer MC
Lien Pubmed
Résumé
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 Ca(2+) release from the InsP3 receptors.
Référence
Biochim. Biophys. Acta. 2017 Jan;:
