Format

Send to

Choose Destination
J Transl Med. 2015 Nov 12;13:356. doi: 10.1186/s12967-015-0727-2.

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.

Author information

1
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110840, China. zhutingzhun2000@aliyun.com.
2
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110840, China. lixm1376212743@aliyun.com.
3
Health Care Centre, Shenyang Entry-Exit Inspection and Quarantine Bureau, Shenyang, China. luolihan258@aliyun.com.
4
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110840, China. littlepig@hotmail.com.
5
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110840, China. lizhiqing@yeah.net.
6
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110840, China. pengxie308@yahoo.com.
7
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110840, China. gaoelmer@hotmail.com.
8
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110840, China. szqlz@163.com.
9
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110840, China. jingyuansu2014@yahoo.com.
10
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110840, China. syjqzyyliangguobiao@yahoo.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.

PMID:
26563263
PMCID:
PMC4642639
DOI:
10.1186/s12967-015-0727-2
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center