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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.

Zhu T, Li X, Luo L, Wang X, Li Z, Xie P, Gao X, Song Z, Su J, Liang G - J Transl Med (2015)

Bottom Line: Western blot analysis was carried out to determine the expression levels of stemness markers, differentiation-related molecules and EMT-related effectors.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, General Hospital of Shenyang Military Area Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110840, China. zhutingzhun2000@aliyun.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

β-Elemene effect on the expression of EMT-related effectors in glioblastoma cells. Cells were treated with β-elemene at various doses for 24 h and analyzed by Western blot. a Compared with the untreated cells, the expression levels of vimentin and E-cadherin were significantly increased whereas the expression levels of N-cadherin and β-catenin were decreased in β-elemene-treated cells in a dose-dependent manner. b The results of (a) were semi-quantitatively estimated using Gel-Pro Analyzer 4.0 software and are illustrated graphically. The results are representative of three independent experiments, and the values are presented as the mean ± SD (*p < 0.05, **p < 0.01)
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Fig5: β-Elemene effect on the expression of EMT-related effectors in glioblastoma cells. Cells were treated with β-elemene at various doses for 24 h and analyzed by Western blot. a Compared with the untreated cells, the expression levels of vimentin and E-cadherin were significantly increased whereas the expression levels of N-cadherin and β-catenin were decreased in β-elemene-treated cells in a dose-dependent manner. b The results of (a) were semi-quantitatively estimated using Gel-Pro Analyzer 4.0 software and are illustrated graphically. The results are representative of three independent experiments, and the values are presented as the mean ± SD (*p < 0.05, **p < 0.01)

Mentions: To evaluate the effect of β-elemene on the expression of EMT-related effectors, G1, G2 and U87 cells were treated with 0, 50, 100 or 200 µg/ml β-elemene for 24 h and Western blot analysis was performed to evaluate vimentin, E-cadherin, N-cadherin and β-catenin expression. The results revealed that β-elemene increased the expression levels of vimentin and E-cadherin and decreased the expression levels of N-cadherin and β-catenin (Fig. 5).Fig. 5


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.

Zhu T, Li X, Luo L, Wang X, Li Z, Xie P, Gao X, Song Z, Su J, Liang G - J Transl Med (2015)

β-Elemene effect on the expression of EMT-related effectors in glioblastoma cells. Cells were treated with β-elemene at various doses for 24 h and analyzed by Western blot. a Compared with the untreated cells, the expression levels of vimentin and E-cadherin were significantly increased whereas the expression levels of N-cadherin and β-catenin were decreased in β-elemene-treated cells in a dose-dependent manner. b The results of (a) were semi-quantitatively estimated using Gel-Pro Analyzer 4.0 software and are illustrated graphically. The results are representative of three independent experiments, and the values are presented as the mean ± SD (*p < 0.05, **p < 0.01)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4642639&req=5

Fig5: β-Elemene effect on the expression of EMT-related effectors in glioblastoma cells. Cells were treated with β-elemene at various doses for 24 h and analyzed by Western blot. a Compared with the untreated cells, the expression levels of vimentin and E-cadherin were significantly increased whereas the expression levels of N-cadherin and β-catenin were decreased in β-elemene-treated cells in a dose-dependent manner. b The results of (a) were semi-quantitatively estimated using Gel-Pro Analyzer 4.0 software and are illustrated graphically. The results are representative of three independent experiments, and the values are presented as the mean ± SD (*p < 0.05, **p < 0.01)
Mentions: To evaluate the effect of β-elemene on the expression of EMT-related effectors, G1, G2 and U87 cells were treated with 0, 50, 100 or 200 µg/ml β-elemene for 24 h and Western blot analysis was performed to evaluate vimentin, E-cadherin, N-cadherin and β-catenin expression. The results revealed that β-elemene increased the expression levels of vimentin and E-cadherin and decreased the expression levels of N-cadherin and β-catenin (Fig. 5).Fig. 5

Bottom Line: Western blot analysis was carried out to determine the expression levels of stemness markers, differentiation-related molecules and EMT-related effectors.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, General Hospital of Shenyang Military Area Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110840, China. zhutingzhun2000@aliyun.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus