• Biomolecules & Therapeutics
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• 제24권4호
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• pp.402-409
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• 2016

It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.

• 대한임상검사과학회지
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• 제51권2호
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• pp.235-244
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• 2019

본 연구는 배양된 C6 신경교종(glioma) 세포에서 환경오염 원인 황산알루미늄에 의한 신경 독성과 파리풀(PLVAH)추출물의 AS에 의해 유도된 신경 독성에 대한 보호효과를 확인해 보았다. 이를 위해 세포생존력과 전자공여(ED)능, 지질과산화(LP) 저해능 및 과산소음이온라디칼(superoxide anion-radical, SAR) 소거능과 같은 항산화효과를 조사하였다. AS는 용량의존적으로 현저히 세포생존율을 감소시켰고 AS의 $XTT_{50}$ 값은 $120.0{\mu}M$로 측정되었다. AS의 신경 독성은 Borenfreund와 Puerner의 독성 기준에 의해 중간 독성으로 판정되었다. 또한, 항산화제인 catalase (CAT)는 AS의 신경독성에 의해 손상된 세포의 생존력을 현저히 증가시켰다. AS 유발 신경 독성에 대한 PLVAH 추출물의 보호 효과에서, PLVAH 추출물은 ED의 능력, LP의 억제 능력 및 SAR 소거능을 유의하게 증가시켰다. 이러한 결과로부터 산화 스트레스가 AS의 세포독성에 관여하고 있으며, PLVAH 추출물의 항산화 작용에 의해 AS에 의해 유도된 신경 독성을 효과적으로 보호한다는 것을 알 수 있었다. PLVAH 추출물과 같은 천연 성분은 산화스트레스를 만드는 AS와 같은 중금속 화합물로 인한 독성을 치료할 수 있는 잠재적 치료제로 가치가 있다고 사료된다.

• 생물정신의학
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• 제12권2호
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• pp.136-142
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• 2005

Object:The intracellular action of the antidepressant, venlafaxine, was studied in C6-gliomas using heat shock protein 70(HSP70) immunocytochemistry and HSP70 Western blots because HSP70 is associated with stress and depression. Methods:To examine how the glucocorticoid affects the expression of HSP70 in nerve cells, the rat C6 glioma cell was treated with dexamethasone for 6 hours. In addition, venlafaxine was administered to the experimental groups of C6 glioma cells for 1, 6, 24, and 72 hours each, after which the expression of HSP70 was investigated. Finally, venlafaxine and dexamethasone were simultaneously administered to the experimental groups for 1, 6, 24, and 72 hours, followed by an investigation of the expression of HSP70. Results:The short term(1 hour) venlafaxine treatment significantly increased the level of HSP70 expression. The short term treatment of venlafaxine with dexamethasone also increased the level of HSP70 expression but this reduction was not statistically significant. The long term(72 hours) venlafaxine with dexamethasone treatment significantly reduced the level of HSP70 expression. The long term treatment of venlafaxine also reduced the level of HSP70 expression but this reduction was not statistically significant. Dexamethasone(10uM, 6hours) did not affect the level of HSP70 expression compared with controls. Conclusion:Venlafaxine increases the expression of HSP70 at short term treatment, but prolonged treatment with dexamethasone suppresses the expression of HSP70.

• 대한한방내과학회지
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• 제27권2호
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• pp.429-443
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• 2006

Objectives : The Purpose of this study was to identify anti-tumor effects of Curcuma longa L. on some kinds of cancer cells through molecular biologic methods. Materials & Methods : We used 4 kinds of cancer cell lines such as glioma cells(A172), cervical cancer cells(HeLa), Prostate cancer cells(PC3), lung cancer cells(A549). We injected the boiled extract of Curcuma longa L. $5{\mu}g,\;10{\mu}g$ to culture media(ml) for 24 hours. We measured the cytotoxic effect on 4 kinds of cancer cells through trypan blue exclusion test and the suppressive effect on viability of 4 kinds of cancer cells via MTT assay. We measured the change of mitochondria membrane potential via flow cytometry. The quantitative RT-PCR was used to examine the effect on the revelation of Bcl-2 and Bax which genes are related to apoptosis. We examined the effect on the revelation of Bcl-2 protein and Bax protein by western blot analysis. Results: 1. Extract of Curcuma longa L. showed significant cytotoxic effect on A172, HeLa, PC3 compared to the control group with density dependent manner. 2. Extract of Curcuma longs L. showed significant suppressive effect on viability of A172, HeLa, PC3 compared to the control group with density dependent manner. 3. Curcuma longs L. induced apoptosis by decreasing the membrane potential of mitochondria in A172, HeLa, PC3. 4. In the test about the revelation of genes related to apoptosis, the revelation of Bcl-2 decreased and the revelation of Bax increased in A172. HeLa, PC3 treated with Curcuma longa L. with density dependent manner. 5. In the test about the revelation of protein related to apoptosis, the protein levels of Bcl-2 decreased and the protein levels of Bax increased in A172, HeLa, PC3 treated with Curcuma longa L. Conclusions: This experiment shewed that Curcuma longs L. has anti-tumor effect on glioma, cervical, Prostate cancer cells except on lung cancer. We hope that anti-tumor effects of Curcuma longa L. will be more Practically identified.

• Journal of Acupuncture Research
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• 제19권5호
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• pp.57-72
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• 2002

Objectives : This study was undertaken to determine the cytotoxic effects of crude bee venom which is widely used for aqua-acupuncture in oriental medical clinic. Methods : We compared the effects of crude bee venom, apamin, melittin and MCD peptide on cellviability by MTT asssay. Results : The obtained results are summarized as follows: 1. Bee venom, apamin, melittin and MCD peptide showed concentration--dependent cytotoxic effect in some human cell lines(human glioma cell line과 neuroblastorna, human mast cell line) for 24 and 48 Hour treatment. 2. Bee venom, apamin, melittin and MCD peptide showed dose-dependent cytotoxic effect in some human cell lines for 24 and 48 Hour treatment. 3. Bee venom treatment for 24 and 48 hour showed higher cytotoxic effects than apamin, melittin and MCD peptide. Conclusions : These results suggest that bee venom, apamin, melittin and MCD peptide have concentration- and dose- dependent cytotoxic effect in some human cell lines. But further study is needed for optimal concentration and dose.

• BMB Reports
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• 제51권10호
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• pp.481-483
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• 2018

Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in human GBM. Our recent study using various sequencing techniques in triple matched samples such as tumor-free SVZ, tumor, and normal tissues from human patients identified the clonal relationship of driver mutations between GBM and tumor-free SVZ harboring neural stem cells (NSCs). Tumor-free SVZ tissue away from the tumor contained low-level GBM driver mutations (as low as 1% allelic frequency) that were found in the dominant clones in its matching tumors. Moreover, via single-cell sequencing and microdissection, it was discovered that astrocyte-like NSCs accumulating driver mutations evolved into GBM with clonal expansion. Furthermore, mutagenesis of cancer-driving genes of NSCs in mice leads to migration of mutant cells from SVZ to distant brain and development of high-grade glioma through the aberrant growth of oligodendrocyte precursor lineage. Altogether, the present study provides the first direct evidence that NSCs in human SVZ is the cell of origin that develops the driver mutations of GBM.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권5호
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• pp.578-581
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• 2008

Schwannoma named neurinoma, peripheral glioma, perineural fibriblastoma and Neurilemmoma is a ectodermal benign neoplasm which originates from schwann cell or neuro axons. It usually develops in peripheral systems of sensory nerves of gastrointestinal tract, oral cavity, and bone. It occurs more frequently in soft tissue than hard tissue, and is extremely rare in intraoral area. We report a case of Schwannoma that showed large mass on buccal cheek with Rt. midfacial swelling, pain, tenderness to palpation and involvement with maxillary branch of trigeminal nerve. We present this case and review the literature.

• 약학회지
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• 제43권1호
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• pp.42-47
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• 1999

Phorbol ester, growth factors activities are mediated by unclear transcription factors, the c-Fos and c-Jun, which can regulate transcriptional activation through specific DNA sites and by forming the transcription factor AP-l, which usually mediates cell proliferation and differentiation signals. We explored effects of Pini Folium extract (API-l) on AP-l activity. Western blot analysis confirmed that API-l decreased levels of c-Fos or c-Jun protein induced by the tumor promoter Phorbol 12-myristate 13-acetate (PMA; 200 nM). Transient transfection assays with a c-fos promoter reporter construct showed that API-l decreased transcription activity by ore than 50~60%. However, treatment of API-l activity studied further. The main substances were fractionated into dichloromethane layer. Futhermore, API-l extract repressed the [$^3H$]-thymidine uptake in C6 glioma cells, indicating that this extract could be included in a new type of modulator in the mitogenesis.

• Journal of Acupuncture Research
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• 제17권4호
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• pp.69-78
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• 2000

Objective : To research the trends of the study related to bee venom and cancer, and to establish the hereafter direction of the study on bee venom herbal acupuncture. Method : We searched in PubMed, with bee venom and cancer(in English, with abstract) Results : 1. We searched 28 Journals, 36 Papers. the frequency of Journals and Papers was as follows: Biochem Biophys Res Commun(4 Papers), FEBS Lett(3), Life Sci, Proc Natl Acad Sci USA, J Immunol(each 2), other 23 Journals(each 1). 2. The pattern of the study was as follows: Review article(3 Journals, 3 Papers), Epidemiologic study(1, 1), Experimental study(24, 32) In vivo 1, 1), In vitto(24, 31) 3. The involved components of bee venom were as follows: Melittin(20), Apamin(8), Phospholipase A2(3), Melittin & Phospholipase A2(3), Melittin& Tertiapin(1). 4. The involved cancer was as follows: leukemia(9), tumor(5), neuroblastoma(4), pituitary tumor and pheochromocytoma(each 3), lymphoma, astrocytoma, glioma and lung cancer(small cell carcinoma)(eacn 2), bladder carcinoma, pancreatic cancer, breast carcinoma, ovarian carcinoma and spuamous cell carcinoma(each 1) Conclusion : We concluded that the most frequent pattern of the study was in vitro experimental study with peptide components of bee venom and the most frequeni invovled cancer was leukemia.

• IMMUNE NETWORK
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• 제5권2호
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• pp.99-104
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• 2005

Background: Malignant gliomas are the most common primary tumors in the central nervous system. Methods: We investigated the combined effect of PG490 and LPS on the induction of the apoptotic pathway in human astroglioma cells. Results: Treatment of U87 cells with combination of 50nM of PG490 and $50{\mu}g/ml$ of LPS resulted in increased internucleosomal DNA fragmentation, cleavage of PLC-${\gamma}1$, and downregulation of cIAP1 and XIAP. The combination of LPS and PG490 treatment-induced apoptosis is mediated through the activation of caspase, which is inhibited by the caspase inhibitor, z-VAD-fmk. Also, release of cytochrome c was found in PG490 and LPS-cotreated U87 cell. Conclusion: Taken together, combination of PG490 and LPS appears to be a potent inducer of apoptosis in astrogliaoma cells, and might have some benefit in the treatment of glioma patients.