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.

Neutralizing gp130 interferes with endothelial-mediated effects on glioblastoma stem-like cells

“…5 We too observed a drastic reduction in the stem-like properties in GSCs treated with the anti-gp130 blocking antibodies, assessed by both tumorsphere formation (Supplementary Figure S1a) and limiting dilution assays (Supplementary Figure S1b), as previously described. 7,8 However, and in contrast to the Shi et al work, no significant impact of anti-gp130 blocking antibodies was observed when GSCs were grown in complete media (Supplementary Figure S1a-b). Moreover, blocking gp130 had no overt impact on cell viability in any of the four GSCs tested (data for GSC4 and GSC9 not shown) in either EC-CM (Supplementary Figure S1c) or complete media (Supplementary Figure S1c).…”

Control of the Endo-Lysosome Homeostasis by the Paracaspase MALT1 regulates Glioma Cell Survival

“…Animal Procedures. Tumor inoculation was performed on female Balb/C nude mice (Janvier) aged 6-7 weeks, as described previously 10 . Animals were randomly assigned to each group and group housed in specific pathogen free (SPF) conditions at 24ºC on a 12-hour daynight cycle.…”

“…GSCs constantly integrate external maintenance cues from their microenvironment, and as such represent the most adaptive and resilient proportion of cells within the tumor mass 5,10 .…”

Review of Natural Product-Derived Compounds as Potent Antiglioblastoma Drugs

“…But blocking apoptosis could not reduce the β -escin-induced effect in sphere formation or stemness marker activity. This result suggests that β -escin directly changes the stem identity of GIC, independent of inducing the cell death [ 66 ]. Acori Graminei Rhizoma is used for traditional medicine, which has beneficial effects on CNS disorders.…”