title: β-escin selectively targets the glioblastoma-initiating cell population and reduces cell viability.
abstract: Glioblastoma multiforme (GBM) is a highly aggressive tumour of the central nervous system and is associated with an extremely poor prognosis. Within GBM exists a subpopulation of cells, glioblastoma-initiating cells (GIC), which possess the characteristics of progenitor cells, have the ability to initiate tumour growth and resist to current treatment strategies. We aimed at identifying novel specific inhibitors of GIC expansion through use of a large-scale chemical screen of approved small molecules. Here, we report the identification of the natural compound β-escin as a selective inhibitor of GIC viability. Indeed, β-escin was significantly cytotoxic in nine patient-derived GIC, whilst exhibiting no substantial effect on the other human cancer or control cell lines tested. In addition, β-escin was more effective at reducing GIC growth than current clinically used cytotoxic agents. We further show that β-escin triggers caspase-dependent cell death combined with a loss of stemness properties. However, blocking apoptosis could not rescue the β-escin-induced reduction in sphere formation or stemness marker activity, indicating that β-escin directly modifies the stem identity of GIC, independent of the induction of cell death. Thus, this study has repositioned β-escin as a promising potential candidate to selectively target the aggressive population of initiating cells within GBM.
authors: CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, F-44000, France.|Team SOAP, "Signaling in Oncogenesis, Angiogenesis, and Permeability", Nantes, F-44000, France.
authors: Elizabeth
authors: E
authors: Harford-Wright
authors: CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, F-44000, France.|Team SOAP, "Signaling in Oncogenesis, Angiogenesis, and Permeability", Nantes, F-44000, France.
authors: Nicolas
authors: N
authors: Bidère
authors: CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, F-44000, France.|Team SOAP, "Signaling in Oncogenesis, Angiogenesis, and Permeability", Nantes, F-44000, France.
authors: Julie
authors: J
authors: Gavard
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000066673:Cell Self Renewal / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004928:Escin / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D004928:Escin
keywords: apoptosis; chemical screen; glioblastoma-initiating cells; self-renewal; temozolomide