Abstract
β-elemene, extracted from herb medicine Curcuma wenyujin has potent anti-tumor effects in various cancer cell lines. However, the activity of β-elemene against glioma cells remains unclear. In the present study, we assessed effects of β-elemene on human glioma cells and explored the underlying mechanism. Human glioma U87 cells were used. Cell proliferation was determined with MTT assay and colony formation assay to detect the effect of β-elemene at different doses and times. Fluorescence microscopy was used to observe cell apoptosis with Hoechst 33258 staining and change of glioma apoptosis and cell cycling were analyzed by flow cytometry. Real-time quantitative PCR and Western-blotting assay were performed to investigated the influence of β-elemene on expression levels of Fas/FasL, caspase-3, Bcl-2 and Bax. The experiment was divided into two groups: the blank control group and β-elemne treatment group. With increase in the concentration of β-elemene, cytotoxic effects were enhanced in the glioma cell line and the concentration of inhibited cell viability (IC50) was 48.5 μg/mL for 24h. β-elemene could induce cell cycle arrest in the G0/G1 phase. With Hoechst 33258 staining, apoptotic nuclear morphological changes were observed. Activation of caspase-3,-8 and -9 was increased and the pro-apoptotic factors Fas/FasL and Bax were upregulated, while the anti-apoptotic Bcl-2 was downregulated after treatment with β-elemene at both mRNA and protein levels. Furthermore, proliferation and colony formation by U87 cells were inhibited by β-elemene in a time and does- dependent manner. Our results indicate that β-elemene inhibits growth and induces apoptosis of human glioma cells in vitro. The induction of apoptosis appears to be related with the upregulation of Fas/FasL and Bax, activation of caspase-3,-8 and -9 and downregulation of Bcl-2, which then trigger major apoptotic cascades.
Highlights
Gliomas are the most common and malignant type of primary brain tumor in adult central nervous system, representing over 50% of all primary intracranial tumors
Our result showed that the effect of antiproliferation and induction of apoptosis were triggered by the induction of Fas/Fas ligand (FasL) and the pro-apoptotic molecules Bax and downregulation of Bcl-2
Curcuma aromatica Salisb is a type of traditional Chinese medicine plant and the essential oils of this plant are widely used in the treatment of cancer (Lu et al, 2012). β-elemene is a sesquiterpene extracted from the soil and is a non-toxic anti-tumor drug where the production is independent research and development in our country. β-elemene can get through the blood-brain barrier and used in the treatment of brain tumor
Summary
Gliomas are the most common and malignant type of primary brain tumor in adult central nervous system, representing over 50% of all primary intracranial tumors. Two main apoptotic pathways have been mentioned as follows: the extrinsic death receptor pathway and the intrinsic mitochondrion pathway (Zhang et al, 2010) Both pathways involve mitochondria and Bcl-2 family protein. The Fas and its Fas ligand (FasL) system play a key role in apoptotic signaling in many cell lines and stimulation of Fas leads to initiating the extrinsic pathway of apoptosis (Wang et al, 2012). FasL is a type II transmembrane protein which binds to its surface receptor Fas to induce apoptotic cell death (Zhang et al, 2010). Our result showed that the effect of antiproliferation and induction of apoptosis were triggered by the induction of Fas/FasL and the pro-apoptotic molecules Bax and downregulation of Bcl-2
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