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Background  Glioblastoma is the most common and lethal type of primary brain tumor.  β -Elemene, a natural plant drug extracted from  Curcuma wenyujin , has shown strong anti-tumor effects in various tumors with low toxicity. However, the effects of  β -elemene on malignant phenotypes of human glioblastoma cells remain to be elucidated. Here we evaluated the effects of  β -elemene on cell proliferation, survival, stemness, differentiation and the epithelial-to-mesenchymal transition (EMT) in vitro and in vivo, and investigated the mechanisms underlying these effects.    Methods  Human primary and U87 glioblastoma cells were treated with  β -elemene, cell viability was measured using a cell counting kit-8 assay, and treated cells were evaluated by flow cytometry. Western blot analysis was carried out to determine the expression levels of stemness markers, differentiation-related molecules and EMT-related effectors. Transwell assays were performed to further determine EMT of glioblastoma cells. To evaluate the effect of  β -elemene on glioblastoma in vivo, we subcutaneously injected glioblastoma cells into the flank of nude mice and then intraperitoneally injected NaCl or  β -elemene. The tumor xenograft volumes were measured every 3 days and the expression of stemness-, differentiation- and EMT-related effectors was determined by Western blot assays in xenografts.    Results   β -Elemene inhibited proliferation, promoted apoptosis, impaired invasiveness in glioblastoma cells and suppressed the growth of animal xenografts. The expression levels of the stemness markers CD133 and ATP-binding cassette subfamily G member 2 as well as the mesenchymal markers N-cadherin and  β -catenin were significantly downregulated, whereas the expression levels of the differentiation-related effectors glial fibrillary acidic protein, Notch1, and sonic hedgehog as well as the epithelial marker E-cadherin were upregulated by  β -elemene in vitro and in vivo. Interestingly, the expression of vimentin was increased by  β -elemene in vitro; this result was opposite that for the in vivo procedure. Inhibiting  β -catenin enhanced the anti-proliferative, EMT-inhibitory and specific marker expression-regulatory effects of  β -elemene.    Conclusions   β -Elemene reversed malignant phenotypes of human glioblastoma cells through  β -catenin-involved regulation of stemness-, differentiation- and EMT-related molecules.  β -Elemene represents a potentially valuable agent for glioblastoma therapy.

journal of translational medicine

Reversion of malignant phenotypes of human glioblastoma cells by β-elemene through β-catenin-mediated regulation of stemness-, differentiation- and epithelial-to-mesenchymal transition-related molecules