• The Journal of Korean Medicine
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• v.30 no.6
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• pp.17-26
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• 2009

Objectives: Little information is available regarding the effect of Lycii cortex radicis (LCR) on cell viability in glioma cells. This study was therefore undertaken to examine the effect of LCR on cell survival in U87MG human glioma cells. Methods: Cell viability and cell death were estimated by MTT assay and trypan blue exclusion assay, respectively. Reactive oxygen species (ROS) generation was measured using the fluorescence probe DCFH-DA. Activation of Akt and extracellular signal-regulated kinase (ERK) and activation of caspase-3 were estimated by Western blot analysis. Results: LCR resulted in apoptotic cell death in a dose- and time-dependent manner. LCR increased reactive oxygen species (ROS) generation and LCR-induced cell death was also prevented by antioxidants, suggesting that ROS generation played a critical role in LCR-induced cell death. Western blot analysis showed that LCR treatment caused down-regulation of Akt and ERK. The LCR-induced cell death was increased by the inhibitors of Akt and ERK. Activation of caspase-3 was stimulated by LCR and caspase inhibitors prevented the LCR-induced cell death. Conclusion: These findings suggest that LCR results in human glioma cell death through a mechanism involving ROS generation, down-regulation of Akt and ERK, and caspase activation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2607-2610
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• 2013

Malignant glioma, also known as brain cancer, is the most common intracranial tumor, having an extremely high mortality and recurrence rate. The survival rate of the affected patients is very low and treatment is difficult. Hence, growth inhibition of glioma has become a hot topic in the study of brain cancer treatment. Among the various isothiocyanate compounds, it has been confirmed that benzyl isothiocyanate (BITC) can inhibit the growth of a variety of tumors, including leukemia, glioma and lung cancer, both inside and outside the body. This study explored inhibitory effects of BITC on human glioma U87MG cells, as well as potential mechanisms. It was found that BITC could inhibit proliferation, induce apoptosis and arrest cell cycling of U87MG cells. In addition, it inhibited the expression of SOD and GSH, and caused oxidative stress to tumor cells. Therefore, it is believed that BITC can inhibit the growth of U87MG cells outside the body. Its mechanism may be related to the fact that BITC can cause oxidative stress to tumor cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.769-773
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• 2015

Fibulin-5 has recently been considered as a potential tumor suppressor in human cancers. Several studies have shown that it is down-regulated in a variety of tumor types and inhibits tumor growth and metastasis. This study was aimed to investigate the clinical significance of fibulin-5 in glioma and its role in cell proliferation and invasion. We found that the expression of fibulin-5 in glioma tissues was significantly lower than those in normal brain (NB) tissues. Negative expression was significantly correlated with advanced clinical stage (grade III+IV). Furthermore, Fibulin-5 negative expression was correlated with a shorter overall survival of glioma patients. Multivariate Cox repression analysis indicated that fibulin-5 was an independent factor for predicting overall survival of glioma patients. Overexpression obviously inhibited cell proliferation in U251 and U87 cells. Furthermore, it significantly reduced the number of migrating and invading glioma cells. In conclusion, impaired expression of fibulin-5 is correlated with the advanced tumor stage in glioma. Otherwise, Fibulin-5 is an independent prognostic marker for predicting overall survival of glioma patients. Mechanistically, it may function as a tumor suppressor via inhibiting cell proliferation and invasion in gliomas.

• The Journal of Korean Medicine
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• v.29 no.1
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• pp.95-105
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• 2008

Objectives : Although herbal medicines containing flavonoids have been reported to exert anti-tumor activities, it has not been explored whether Hwang-Jeong (Polygonati sibirici Rhizoma, PsR) exerts anti-tumor activity in human glioma. The present study was therefore undertaken to examine the effect of PsR on cell viability and to determine its underlying mechanism in A172 human glioma cells. Methods : Cell viability was estimated by MTT assay. Reactive oxygen species generation and mitochondrial membrane potential were measured by the fluorescence dyes. The phosphorylation of kinases was evaluated by western blot analysis and caspase activity was estimated using colorimetric assay kit. Results : PsR resulted in loss of cell viability in a dose- and time-dependent manner. PsR did not increase reactive oxygen species (ROS) generation and the PsR-induced cell death was also not affected by antioxidants, suggesting that ROS generation is not involved in loss of cell viability. Western blot analysis showed that PsR treatment caused rapid reduction in phosphorylation of extracellular signal-regulated kinase (ERK) without changes in p38 and Jun-NH2-terminal kinase (JNK). U0126, an inhibitor of ERK, increased the PsR-induced cell death, but inhibitors of p38 and JNK did not affect the cell death. PsR induced depolarization of mitochondrial membrane potential. Caspase activity was not stimulated by PsR and caspase inhibitors did not prevent the PsR-induced cell death. Conclusion : Taken together, these findings suggest that PsR results in human glioma cell death through caspaseindependent mechanisms involving down-regulation of ERK.

• BMB Reports
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• v.54 no.12
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• pp.601-607
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• 2021

Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors (GPCRs). OR expression outside of the nose has functions distinct from odor perception, and may contribute to the pathogenesis of disorders including brain diseases and cancers. Glioma is the most common adult malignant brain tumor and requires novel therapeutic strategies to improve clinical outcomes. Here, we outlined the expression of brain ORs and investigated OR expression levels in glioma. Although most ORs were not ubiquitously expressed in gliomas, a subset of ORs displayed glioma subtype-specific expression. Moreover, through systematic survival analysis on OR genes, OR51E1 (mouse Olfr558) was identified as a potential biomarker of unfavorable overall survival, and OR2C1 (mouse Olfr15) was identified as a potential biomarker of favorable overall survival in isocitrate dehydrogenase (IDH) wild-type glioma. In addition to transcriptomic analysis, mutational profiles revealed that somatic mutations in OR genes were detected in > 60% of glioma samples. OR5D18 (mouse Olfr1155) was the most frequently mutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDH wild-type-specific mutation. Based on this systematic analysis and review of the genomic and transcriptomic profiles of ORs in glioma, we suggest that ORs are potential biomarkers and therapeutic targets for glioma.

• Archives of Pharmacal Research
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• v.20 no.4
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• pp.379-383
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• 1997

Cyclosporin A, an potent immunosuppressant, has been known to be one of the modulators of drug resistance as well as a cytostatic drug. Despite many attempts to basic or clinical application of cyclosporin A, there are few reports on the inhibition of brain tumor cells. In the present experiment, the possibility of cyclosporin A as synergic adjuvant was investigated by MTT assay, $[^{3}H]$ thymidine uptake and through flowcytometric anaysis. Sole treatment of cyclosporin A on the CRT and CH235-MG glioma cell line revealed dose dependent cytotoxicity within a range of tested dose. Combined treatment of cyclosporin A with ACNU, BCNU and hydroxyurea on various glioma cancer cell line led to a significant synergistic cytotoxicity as well as inhibition of DNA synthesis with dose-dependency. In addition, cyclosporin A alone or combined treatment caused discernible changes of cell cycle in the tested cells. These data provide that cyclosporin A could potentiate the effect of nitrosourea compounds in vitro on human glioma cells.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.105-105
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• 2001

In an attempt to provide useful information on the development of an artifitial nerve tubing, proliferative and migrative properties of two glioma cell lines, C6 rat glioma cells and Hs683 human glioma cells, were examined. The present study shows that C6 cells proliferated more rapidly than Hs683 cells. The Hs683 cells are more adequate for the development of nerve tubing since unlike C6 cells, they are of human origin and known to be non-tumorigenic. In order to enhance proliferative and migrative abilities of Hs683 cells for the application as an artificial nerve tubing, we studied the effect of glial cell-derived neurotrophic factor (GDNF) on Hs683 cells. Cells were seeded in the scaffolds (polymer constructs), fabricated with type I collegen and alginate modified with cinnamoyl moiety, in the presence or absence of GDNF Stimulatory effect of GDNF on the proliferation and migration of Hs683 cells cultured in the scaffolds is currently under investigation. In addition, possible neuroprotective activities of natural products which inhibit staurosporine-induced apoptosis of glioma cells are also being studied.

• Journal of Korean Biological Nursing Science
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• v.7 no.1
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• pp.47-56
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• 2005

nm23-H1 gene expression has been inversely correlated with tumor metastatic potential in certain tumors including melanomas, breast carcinomas, and hepatocellular carcinomas. However, its role with respect to the invasive behavior of central nervous system tumors has scarcely been addressed Because cell motility and invasion plays an essential role in metastatic dissemination, we have studied whether motile human glioma cell(U87MG) transfected with nm23-H1 complementary DNA have any alterations in their ability to migrate and invade. There was no significant changes in the shape and size of the cells following nm23-H1 transfection. The role of nm23-H1 in glioma migration and invasion have been evaluated by in vitro simple scratch technique and brain slice invasion model Basal migration ability of nm23-H1 transfectants cell(U87MG-pEGFP-nm23) were lesser than U87MG. Accordingly, U87MG-pEGFP-nm23 didn't migrate away apparently from the tumors implanted site comparing U87MG in brain slice invasion model. These results suggest that nm23-H1 may play an important role in suppressing the human glioma migration and invasion.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.4
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• pp.888-894
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• 2009

It has been reported that silibinin, a natural polyphenolic flavonoid, induces cell death in various cancer cell types. However, the underlying mechanisms by which silibinin induces apoptosis in human glioma cells are poorly understood. The present study was therefore undertaken to examine the effect of silibinin on glioma cell apoptosis and to determine its underlying mechanism in human glioma cells. Apoptosis was estimated by FACS analysis. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (${\Psi}m$) were measured using fluorescence dyes DCFH-DA and $DiOC_6$(3), respectively. Cytochrome c release from mitochondria and caspase-3 activation were estimated by Western blot analysis using specific antibodies. Exposure of cells to 30 mM silibinin induced apoptosis starting at 6 h, with increasing effects after 12-48h in a time-dependent manner. Silibinin caused ROS generation and disruption of ym, which were associated with the silibinin-induced apoptosis. The silibinin-induced ROS generation and disruption in ym were prevented by inhibitors of mitochondrial electron transport chain. The hydrogen peroxide scavenger catalase blocked ROS generation and apoptosis induced by silibinin. Silibinin induced cytochrome c release into cytosolic fraction and its effect was prevented by catalase and cyclosporine A. Silibinin treatment caused caspase-3 activation, which was inhibited by DVED-CHO and cyclosporine A. Pretreatment of caspase inhibitors also protected against the silibinin-induced apoptosis. These findings indicate that ROS generation plays a critical role in the initiation of the silibinin-induced apoptotic cascade by mediation of the mitochondrial apoptotic pathway including the disruption of ${\Psi}m$, cytochrome c release, and caspase-3 activation.

• Journal of Korean Neurosurgical Society
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• v.67 no.3
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• pp.364-375
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• 2024

Objective : Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. Methods : Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. Results : The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. Conclusion : Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.