beta-escin and Brain-Neoplasms

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.

Topics: Aged; Apoptosis; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Self Renewal; Cell Survival; Escin; Female; Glioblastoma; Humans; Male; Middle Aged; Molecular Structure; Neoplastic Stem Cells; Tumor Cells, Cultured

Topics: Brain Edema; Brain Neoplasms; Drug Evaluation; Escin; Humans; Injections, Intravenous; Intracranial Pressure; Preoperative Care; Saponins

Topics: Aesculus; Animal Experimentation; Animals; Brain Diseases; Brain Neoplasms; Cerebrospinal Fluid; Cerebrospinal Fluid Pressure; Escin; Humans; Intracranial Pressure; Saponins