• Journal of Ginseng Research
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• 제32권1호
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• pp.62-66
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• 2008

Non-saponin gingseng fraction components (NSRG) have been known to have a variety of biological activity. However, the effects of these components on the function of brain cell have not been characterized in detail. In this study, we investigated the preventive effect of non-saponin red ginseng components on acrylamide (ACR)-induced suppression of neural cell adhesion molecule (NCAM), which is highly expressed in neuronal cells. The data showed that NSRG blocked the suppression of NCAM expression by ACR in neuroblastoma cells (SK-N-SH). In addition, NSRG significantly increased NCAM expression in ACR-nontreated neuroblastoma cells. NSRG treatment resulted in the increase of cell proliferation in a concentration-dependent manner. We also examined whether NSRG could modulate the NO production of astrocytes. When glioma cells (C6) were treated with various concentrations of NSRG (100-300 ug/ml) in the presence or absence of $IFN-{\gamma}$ for 24 hours, NO production was suppressed in $IFN-{\gamma}-$stimulated C6 cells. Taken together, these results demonstrate that treatment of brain cells with NSRG results in the enhancement of proliferation, the suppression of NO production and the protective effect on NCAM expression impaired by ACR. Thus, the present data suggest that NSRG has proliferative and neuroprotective effects and these effects could be useful in neuronal diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.309-314
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• 2013

Aim: Brain tumors almost universally have fatal outcomes; new therapeutics are desperately needed and will only come from improved understandins of glioma biology. Methods: Exosomes are endosomally derived 30~100 nm membranous vesicles released from many cell types. Examples from GL26 cells were here purified using density gradient ultracentrifugation and monitored for effects on GL26 tumor growth in C57BL/6j mice (H-2b). Lactate dehydrogenase release assays were used to detect the cytotoxic activity of CD8+T and NK cells. Percentages of immune cells producing intracellular cytokines were analyzed by FACS. Results: In this study, exosomes from murine-derived GL26 cells significantly promoted in vivo tumor growth in GL26-bearing B6 mice. Then we further analyzed the effects of the GL26 cells-derived exosomes on immune cells including CD8+T, CD4+T and NK cells. Inhibition of CD8+T cell cytotoxic activity was demonstrated by CD8+T cell depletion assays in vivo and LDH release assays in vitro. The treatment of mice with exosomes also led to a reduction in the percentages of CD8+T cells in splenocytes as determined by FACS analysis. Key features of CD8+T cell activity were inhibited, including release of IFN-gamma and granzyme B. There were no effects of exosomes on CD4+T cells and NK cells. Conclusion: Based on our data, for the first time we demonstrated that exosomes from murine derived GL26 cells promote the tumor growth by inhibition of CD8+T cells in vivo and thus may be a potential therapeutic target.

• Biomolecules & Therapeutics
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• 제23권4호
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• pp.367-373
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• 2015

Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.

• 동의생리병리학회지
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• 제23권5호
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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 Korean Neurosurgical Society
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• 제38권1호
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• pp.12-15
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• 2005

Objective : Cerebral edema develops in the brain tumors by loosening of the endothelial tight junction. Tight junction[TJ] proteins, such as occludin and claudin bind adjacent cells tightly. Authors examine the expression rate of occludin in human brain tumors to evaluate the effect of altered expression of occludin on cerebral edema. Methods : Seventy surgical specimens stored at $-70^{\circ}C$ were used. It included 14 astrocytic tumors, 27 meningiomas, 12 scwannomas, 7 pituitary adenomas, 6 hemangioblastomas. and 4 craniopharyngiomas. After protein extraction, expression of occludin was investigated by Western blot analysis. The tumors were classified according to World Health Organization[WHO] classification. Results : The expression rates of occludin in brain tumors were : glioma [8/14=57.1%]. meningioma [16/27=59.3%], schwannoma [10/12=83.3%], pituitary adenoma [6/7=85.7%], hemangioblastoma [6/6=100%], and craniopharyngioma [3/4=75.0%]. The expression rate in glioma and meningioma was lower than other brain tumors. In gliomas, high grade tumor [1/4=25.0%] exhibited lower expression rate of occludin than low grade one [7/10=70.0%]. Conclusion : These results suggest that the expression of occludin is different among the various kinds of brain tumors. In gliomas, its expression is correlated with the histological grade. It may indicate that occludin plays a role in the development of edema in the brain tumors.

• 대한의생명과학회지
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• 제23권4호
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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.

• 대한본초학회지
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• 제24권1호
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• pp.23-33
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• 2009

Objectives : The present study was performed to clarify the antioxidant and anticancer effects of extract of stamens of Nelumbo nucifera and Kaempferol. Methods : Antioxidant effect was measured by DPPH-radical scavenging activity for electron donating ability (EDA), superoxide dismutase (SOD)-like activity for SOD and lipid peroxidation. Anticancer effect was assessed by MTT absorbance for cytotoxicity. Results : Vitamin E, Kaempferol and ethyl acetate extract of stamens of Nelumbo nucifera increased SOD-like activity and DPPH-radical scavenging activity dose-dependently. On the contrary, lipid peroxidation was time-dependently decreased. Furthermore, Kaempferol and ethyl acetate extract of stamens of Nelumbo nucifera significantly decreased the growth rate of C6 glioma cells. Conclusions : These results suggest that ethyl acetate extract of stamens of Nelumbo nucifera may be a putative antioxidant or anticancer substance.

• 대한임상검사과학회지
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• 제52권2호
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• pp.150-157
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• 2020

본 연구는 이산화망간(MnO₂)의 신경독성과 이에 대한 노박 덩굴 추출물의 보호 효과를 C6 glioma 세포를 배양하여 조사하였다. 본 연구를 위하여 세포생존율을 비롯하여 지질산화(LP) 억제능 및 XO 저해능과 같은 항산화 분석을 시행하였다. 그 결과 MnO₂는 배양 세포에 처리한 농도에 비례하여 세포생존율을 유의하게 감소시켰으며, 이 과정에서 XTT₅₀값은 146.7 μM로 나타나 Borenfreund and Puerner의 독성판정기준에 따라 중간독성(mid-cytotoxic)인 것으로 나타났다. 또한, 항산화제의 일종인 kaempferol (KAE)은 MnO₂의 독성에 의해 손상받은 세포의 생존율을 유의하게 증가시킴으로써 MnO₂의 독성을 방어하였다. 한편, MnO₂ 독성에 대한 노박덩굴(CO) 추출물의 영향 조사에 있어서, CO 추출물은 배양 세포에 MnO₂만을 처리한 것에 비하여 세포생존율을 유의하게 증가시킴으로써 MnO₂의 독성을 효과적으로 방어하였다. 이와 동시에 높은 LP 억제능과 XO 저해능과 같은 항산화 효과를 보여주었다. 이상의 결과에서 MnO₂의 독성에 산화적 손상이 관여하고 있음을 알 수 있었으며, CO 추출물은 LP 억제능과 XO 저해능과 같은 항산화능에 의하여 MnO₂의 독성을 효과적으로 방어한 것을 확인였다. 따라서, CO 추출물과 같은 천연소재는 파킨슨병 유발제인 MnO₂와 같이 산화적 손상과 관련된 질환적 중금속 독성을 경감 내지는 개선할 수 있는 유용한 물질이라 생각된다.

• Bulletin of the Korean Chemical Society
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• 제25권8호
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• pp.1147-1150
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• 2004

Hypericin (1,3,4,6,8,13-hexahydroxy-10,11-dimethylphenanthro[1,10,9,8-opqra]perylene-7,14-dione), an antidepressant which is also known to be a potent protein kinase C (PKC) inhibitor was synthesized as a precursor for radioiodine labeling via two step reactions. Malignant glioma cells express higher PKC activity compared to untransformed glial cell. Here we report the synthesis and radioiodine labeling of hypericin as a potential brain tumor imaging radiopharmaceutical. The reference compound, 2-iodohypericin, and its radiolabelled analogues, 2-[$^{123}I$]iodohypericin and 2-[$^{124}I$]iodohypericin have been prepared by the reaction of hypericin with NaI or [$^{123}I$]NaI or [$^{124}I$]NaI. The labeling yield was 60-65% for each analogue and the optimal reaction time was 10 min. The purification and isolation of the labelled products were achieved by a reversed-phase HPLC.

• 생물정신의학
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• 제14권2호
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• pp.115-121
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• 2007

연구목적: 알코올의존에 내재된 분자생물학적 기전을 이해하고 알코올리즘 치료 약물의 새로운 표적을 알아내기 위해서는, 알코올에 반응하는 유전자 혹은 반응 경로를 알아내는 것이 필요하다. DNA microarray 기법의 발달로 고전적 연구 방법과 달리 동시에 수천 수만개의 유전자의 표현을 검사하는 것이 가능하게 되었다. 본 연구에서는 알코올을 흰쥐의 신경아교종 세포에 처리했을 때 어떤 유전자의 발현을 조절하는지 DNA microarray를 이용하여 알아보고자 하였다. 방 법: 흰쥐 신경아교종 C6 세포주를 배양하여 에탄올 처리하고 총 RNA를 분리한 후 유전자 발현 양상을 조사하기 위해 cDNA microarray를 수행하였다. 결 과: 에탄올 처리군과 대조군간의 유전자 발현의 차이를 비교 분석한 결과 에탄올이 처리된 군에서 대조군에 비해 15개의 유전자가 발현이 증가하였고 12개의 유전자가 발현이 감소하였다. 발현이 증가한 유전자는 Orthodenticle(Drosophila) homolog 1, procollagen type II, adenosine A2a receptor, GATA-bindning protein2를 포함하고 있었고, 발현이 감소한 유전자는 diacylglycerol kinase beta, PRKC, Protein phosphatase 1, clathrin-associated protein 17, nucleoporin p58, proteasome를 포함하였다. 결 론: 흰쥐의 신경아교종 세포주에 알코올을 처치하였을 때 급성기에 알코올에 반응하여 발현이 증가하거나 감소한 유전자는 전반적으로 전사의 조절, 신호전달체계, 허혈성 뇌손상의 중재, 신경세포의 퇴행에 관여하는 것들이었다. 본 연구는 유전자 발현 시스템을 이용하여 에탄올에 반응하는 새로운 후보 유전자들을 관찰하였다는데 의의가 있다.