• Biomedical Science Letters
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• v.23 no.4
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• pp.339-347
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• 2017

This study was performed to evaluate the cytotoxicity induced by ischemia-like condition (ILC) in cultured neuroglial cells (C6 glioma cells). The protective effect of kaempferol (KAE), flavonoid against the cytotoxicity induced by ILC induction was assessed. In addition, antioxidative effects of KAE were done by colorimetric assays. Cell viability and the antioxidative effects such as DPPH-radical scavenging activity, superoxide dismutase (SOD)-like activity and inhibitory activity of lipid peroxidation (LP) were analyzed. ILC induction decreased cell viability in a dose-dependent manner, and the $XTT_{90}$ value (low cytotoxicity value) and $XTT_{50}$ value (high cytotoxicity value) were determined during ILC induction for 15 and 40 minutes, respectively. The butylated hydroxytoluene (BHT) antioxidant significantly increased cell viability damaged by the ILC-induced cytotoxicity. In the protective effect of KAE on ILC-induced cytotoxicity, KAE protected the ILC-induced cytotoxicity by the significant increase of cell viability, and also it showed DPPH-radical scavenging ability, SOD-like ability and inhibitory ability of LP. From these results, it is suggested that ILC induction showed cytotoxicity in these cultures and the oxidative stress is involved in the ILC-induced cytotoxicity. While, KAE prevented ILC-induced cytotoxicity by antioxidative effects. In conclusion, natural products like KAE may be a putative therapeutic agent for the treatment of disease associated with oxidative stress such as ischemia.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.2
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• pp.150-157
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• 2020

The protective effects of a Celastrus orbiculatus Thunb (CO) extract against manganese dioxide (MnO₂)-induced cytotoxicity in cultured C6 glioma cells were examined. This study assessed the antioxidative effects, including the suppressive ability of lipid peroxidation (LP), the inhibitory ability of xanthine oxidase (XO), and the cell viability. MnO₂ decreased the cell viability remarkably in a dose-dependent manner. The XTT₅₀ value was determined to be 146.7 μM in these cultures. The cytotoxicity of MnO₂ was calculated to be mid-toxic using Borenfreund and Puerner's toxic criteria. Kaempferol (KAE) increased the cell viability damaged by MnO₂-induced cytotoxicity significantly. Regarding the protective effects of the CO extract on MnO₂-induced cytotoxicity, the CO extract increased cell viability significantly compared to the MnO₂-treated group. The CO extract also had inhibitory abilities against lipid peroxidation (LP) and xanthine oxidase (XO). From these findings, oxidative stress is involved in the cytotoxicity of MnO₂. The CO extract effectively blocked the cytotoxicity induced by MnO₂ via its antioxidative effects. Conclusively, natural resources, such as the CO extract, might be a useful agent for the diminution or improvement of the heavy metal cytotoxicity correlated with disease through oxidative stress, such as MnO₂, a Parkinsonism inducer.

• The Journal of Internal Korean Medicine
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• v.21 no.3
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• pp.467-475
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• 2000

The water extracts of Jagamcho-tang has been used for treatment of arrhythmia and palpitation in oriental traditional medicine. Brain is provided with blood flow by heart. Jagamcho-tang has been studied on ischemia and infarction in heart. However, little is known about the mechanism by which the water extracts of Jagamcho-tang rescues brain cells from ischemic damages. To elucidate the protective mechanism on ischemic induced cytotoxicity, the effects of Jagamcho-tang on ischemia induced cytotoxicity and generation of nitric oxide(NO) are investigated in C6 glioma cells. Jagamcho-tang induce NO in a dose dependent manner up to 2.5mg/ml in C6 glioma cells. The pretreatment of Jagamcho-tang protect sodium nitroprusside(SNP) (2mM) induced cytotoxicity. This effect of Jagamcho-tang is mimicked by treatment by pretreatment of SNP($100{\mu}M$), an exogenous NO donor. NG-monomethyl-L-arginine($N^{G}MMA$), a specific inhibitor of nitric oxide synthase (NOS), significantly blocks the protective effects of Jagamcho-tang on cell toxicity by ischemia. In addition, lipopolysaccharide(LPS) and phorhol 12 myristate 13-acetate(PMA) treatment for 72h in C6 glial cells markedly induce NO, but treatment of the cells with the water extracts of Jagamcho-tang decrease nitrite formation in a dose dependent manner. In addition, LPS and PMA treatment for 72h induce severe cell death and LDH release into medium in C6 glial cells. However treatment of the cells with the water extracts of Jagamcho-tang dose not induce significant changes compare to control cells. Furthermore, the protective effects of the water extracts of Jagamcho-tang is mimicked by treatment of $N^{G}MMA$. Taken together, I suggest that the protective effects of the water extracts of Jagamcho-tang against ischemic brain damages may be mediated by regulation of iNOS during ischemic condition.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.29-35
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• 2019

Decursin is a major biological active component of Angelica gigas Nakai and is known to induce apoptosis of metastatic prostatic cancer cells. Recently, other reports have been commissioned to examine the anticancer activities of this plant. In this study, we evaluated the inhibitory activity and related mechanism of action of decursin against glioblastoma cell line. Decursin demonstrated cytotoxic effects on U87 and C6 glioma cells in a dose-dependent manner but not in primary glial cells. Additionally, decursin increased apoptotic bodies and phosphorylated JNK and p38 in U87 cells. Decursin also down-regulated Bcl-2 as well as cell cycle dependent proteins, CDK-4 and cyclin D1. Furthermore, decursin-induced apoptosis was dependent on the caspase activation in U87 cells. Taken together, our data provide the evidence that decursin induces apoptosis in glioblastoma cells, making it a potential candidate as a chemotherapeutic drug against brain tumor.

• Journal of Acupuncture Research
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• v.19 no.3
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• pp.41-50
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• 2002

Objective : To study anti-inflammatory, analgesic effect and molecular biological mechanism of honey bee venom for aqua-acupuncture, human mast cell line(HMC-1) and human glioma cell line(HS683) were treated with bee venom. Methods : Cell viability of bee venom was tested by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) asssay. To explore whether anti-inflammatory, analgesic effects of bee venom are associated with the control of gene expression, quantitative RT-PCR analysis of inflammation and pain related genes was performed. Results : The MTT assay demonstrated that cell viability was not decreased by treatment with 10-9 ug/ml bee venom in comparison with 10-2, 10-3, 10-4, 10-5, 10-6, 10-7, 10-8, 10-9, 10-10 and 10-11 ug/ml. sPLA2 and COX-l were down-regulated by treatment with 10-9 ug/ml bee venom in HS683 Cell line in comparison with control. COX-2 was up-regulated by treatment with 10-9 ug/ml bee venom in HS683 Cell line and HSP-2 was up-regulated by treatment with 10-9 ug/ml bee venom in HMC-1 Cell line in comparison with control. sPLA2, COX-1 and COX-2 showed no significant regulation in HMC-1 Cell line and cPLA2 also showed no significant regulation in both HMC-l and HS683 Cell line between control and bee venom treated group.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.969-973
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• 2009

Samul-tang (SMT), which was firstly described in (Hwajegukbang) Song dynasty, is well known remedy for blood diseases in Oriental medicine. SMT is traditional herbal-remedy composed of Rehmanniae Radix Preparat, Angelicae Gigantis Radix, Cnidii Rhizoma and Paeoniae Radix. Recently, SMT has known to have anti-oxidative action. However, the reports on anti-oxidantic action in neuroglial cells are rare. In addition, the exact mechanisms are unclear. For these reasons, we investigated the protective effects of SMT on cell death induced by oxidative stress using C6 glioma cells. In our results, SMT accelerated proliferation rates of C6 cells in vitro. In addition, levels of LDH release induced by oxidative stress were lowered by treatment with SMT. Finally, protective effects on cell death induced by chemicals such as paraquat and rotenone were observed. In conclusion, these results suggest the possibility to protect brain cell or neuronal cell from damage induced by oxidative stress.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.5
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• pp.1249-1253
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• 2006

The fractions of Capsosiphon fulvescens were studied to verify the anticancer and immunostimulating activity. The fractions from the ethanol extract of C. fulvescens were prepared by the systematic extraction procedure with the solvents such as hexane, ethyl ether, methanol, butanol and H$_2$O. The cytotoxic effects of C. fulvescens fractions against human leukemia cell line U937, mouse neuroblastoma cell line (NB41A3), human hepatoma cell line (HepG2)and rat glioma cell line (C6) were investigated. Ethyl ether fraction of C. fulvescens showed the highest cytotoxicity against all four cell lines tested. In addition, H$_2$O fraction also showed relatively high cytotoxicity. Dose dependent patterns were observed on all four cell lines. The immune-stimulating effects of C. fulvescens fractions on rat macrophage cell line (RAW 264.7) were also investigated. All five fractions of C. fulvescens extract stimulated NO production with concentration dependant manner. These results suggest that C. fulvescens may be a useful candidate for a natural antitumor and immune-stimulating agent.

• Journal of Korean Neurosurgical Society
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• v.40 no.4
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• pp.217-226
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• 2006

Malignant gliomas are the most common type of primary brain tumor and are in great need of novel therapeutic approaches. Advances in treatment have been very modest, significant improvement in survival has been lacking for many decades, and prognosis remains dismal. Despite "gross total" surgical resections and currently available radio-chemotherapy, malignant gliomas inevitably recur due to reservoirs of notoriously invasive tumor cells that infiltrate adjacent and non-adjacent areas of normal brain parenchyma. In principle, the immune system is uniquely qualified to recognize and target these infiltrative pockets of tumors cells, which have generally eluded conventional treatment approaches, In the span of the last 10 years, our understanding of the cancer-immune system relationship has increased exponentially; and yet we are only beginning to tease apart the intricacies of the central nervous system and immune cell interactions. This article reviews the complex associations of the immune system with brain tumors. We provide an overview of currently available treatment options for malignant gliomas, existing gaps in our knowledge of brain tumor immunology, and strategies that might be exploited for improved design of "custom immunotherapeutics." We will also examine major new immunotherapy approaches that are being actively investigated to treat patients with malignant glioma, and identify some current and future research priorities in this area.

• Journal of Acupuncture Research
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• v.20 no.2
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• pp.173-183
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• 2003

이 논문(論文)은 활성 산소(ROS)의 작용(作用)을 규명하고 호도약침액(胡桃藥鍼液)이 인간의 신경교종 세포인 A172에서 화학적(化學的) 저산소증(低酸素症)으로 유발된 세포 사멸에 대해 효능이 있는지를 연구(硏究)한 것이다. 화학적(化學的) 저산소증(低酸素症)은 세포내 미토콘드리아의 전자 수송을 방해하는 antimycin A를 가진 배양세포에 의해 유발(誘發)하였다. 화학적(化學的) 저산소증(低酸素症)에 노출된 세포(細胞)는 시간과 그 양에 따라서 세포 사멸의 결과(結果)가 다르게 나타난다. 화학적 저산소증에 의해서 ROS의 생산이 증가하는데 이것은 $H_2O_2$ 소거(消去) Catalase(과산화수소를 물과 산소로 분해하는 효소)에 의해 방지(防止)된다. Catalase는 화학적 저산소증에 의해 유발(誘發)된 세포 사멸을 방지하는데 비해 DMTU는 효과적이지 않다. 지질(脂質)에 녹는 산화방지제 DPPD와 물에 녹는 산화방지제 Trolox는 세포사멸을 방지하는데 효과(效果)가 없다. 호도약침액(胡桃藥鍼液)은 그 양(量)에 의존적으로 저산소증에 의해 유발된 세포 사멸을 방지하는 효과가 있다. 즉 화학적 저산소증으로 유도된 ROS의 발생을 막고, $H_2O_2$로 유도된 세포사멸을 방지하는데 이것은 화학적 저산소증과 $H_2O_2$의해 유도된 세포사멸에 대해 호도약침액(胡桃藥鍼液)이 방지효과(防止效果)가 있다는 것을 의미한다. 이러한 결과(結果)들은 $H_2O_2$가 지질 과산화와는 무관한 메카니즘으로 저산소증(低酸素症)으로 유발(誘發)된 세포사멸을 중재하고, 따라서 호도약침액(胡桃藥鍼液)은 지질막의 과산화를 방지하기 보다는 ROS를 직접적으로 소거(消去)함으로써 방지 효과가 있다는 것을 의미한다. 더구나 화학적(化學的) 저산소증(低酸素症)은 caspase와 무관한 메카니즘으로 apoptosis를 유발(誘發)한다.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4101-4106
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• 2013

Alterations of cyclin D1, one of the main regulators of the cell cycle, are known to be involved in various cancers. The CCDN1 G870A polymorphism causes production of a truncated variant with a shorter half-life and thus thought to impact the regulatory effect of CCDN1. The aim of the present study was to contribute to existing results to help to determine the prognostic value of this specific gene variant and evaluate the role of CCDN1 G870A polymorphism in brain cancer susceptibility. A Turkish study group including 99 patients with primary brain tumors and 155 healthy controls were examined. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The CCDN1 genotype frequencies in meningioma, glioma and control cases were not significantly different (p>0.05). No significant association was detected according to clinical parameters or tumor characteristics; however, a higher frequency of AG genotype was recorded within patients with astrocytic or oligoastrocytic tumors. A significant association between AG genotype and gliobilastoma multiforme (GBM) was recorded within the patients with glial tumors (p value=0.048 OR: 1.87 CI% 1.010-3.463). According to tumor characteristics, no statistically significant difference was detected within astrocytic, oligoasltrocytic tumors and oligodentrioglias. However, patients with astrocytic astrocytic or oligoastrocytic tumors showed a higher frequency of AG genotype (50%) when compared to those with oligodendrioglial tumors (27.3%). Our results indicate a possible relation between GBM formation and CCDN1 genotype.