• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2151-2157
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• 2016

Scabraside D, a sulfated triterpene glycoside, was extracted from the sea cucumber Holothuria scabra. It shows anti-proliferation in many of cancer cell lines, but the function and mechanisms of action of scabraside D in human cholangiocarcinoma (HuCCA) have not previously determined. In this study, we investigated the activity of scabraside D on HuCCA cell apoptosis, lymphangiogenesis and metastasis in a nude mouse model. Scabraside D induced signs of apoptosis, such as cell shrinkage, nuclear condensation, nuclear fragmentation and DNA fragmentation on TUNEL assays, while effectively decreasing expression of BCl-2 but increasing caspase-3 gene level expression. Immunohistochemistry revealed that scabraside D significantly reduced lymphatic vessel density (LVD). Moreover, scabraside D treatment significantly decreased VEGF-C, MMP-9 and uPA gene expression, which play important roles in the lymphangiogenesis and invasion of cancer cells in metastasis processes. Quantitative real-time PCR showed that scabraside D significantly decreased iNOS and STAT-3 gene expression. This study demonstrated that scabraside D plays a role in activation of HuCCA tumor apoptosis and inhibition of lymphangiogenesis, invasion and metastasis through decreasing BCl-2, MMP-9, uPA and VEGF-C and increasing caspase-3 expression by suppression of iNOS and STAT-3 expression. Therefore, scabraside D could be a promising candidate for cholangiocarcinoma treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2439-2445
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• 2014

Cryptotanshinone (CPT), is a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miotiorrhiza bunge. Numerous researchers have found that it could work as a potent antitumor agent to inhibit tumor growth in vitro, buith there has been much less emphasis on its in vivo role against breast tumors. Using a mouse tumor model of MCF7 cells, we showed that CPT strongly inhibited MCF7 cell growth in vivo with polarization of immune reactions toward Th1-type responses, stimulation of naive CD4+ T cell proliferation, and also increased IFN-${\gamma}$ and perforin production of CD4+ T cells in response to tumor-activated splenocytes. Furthermore, data revealed that the cytotoxic activity of CD4+ T cells induced by CPT was markedly abrogated by concanamycin A(CMA), a perforin inhibitor, but not IFN-${\gamma}$ Ab. On the other hand, after depletion of CD4+ T cells or blocked perforin with CMA in a tumor-bearing model, CPT could not effectively suppress tumor growth, but this phenomenon could be reversed by injecting naive CD4+ T cells. Thus, our results suggested that CPT mainly inhibited breast tumor growth through inducing cytotoxic CD4+ T cells to secrete perforin. We further found that CPT enhanced perforin production of CD4+ T cells by up-regulating JAK2 and STAT4 phosphorylation. These findings suggest a novel potential therapeutic role for CPT in tumor therapy, and demonstrate that CPT performs its antitumor functions through cytotoxic CD4+ T cells.

• Clinical and Experimental Pediatrics
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• 제53권4호
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• pp.592-597
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• 2010

고 IgE 증후군은 만성 습진성 피부병변, 반복적인 호흡기 감염과 고 IgE 혈증이 특징인 드문 면역결핍질환이다. 환아는 객혈을 주소로 내원한 16세 여아로, 과거력상 신생아시기서부터 시작된 반복적인 피부발진, 잦은 상기도 감염 및 폐렴으로 외부병원에서 지속적인 치료를 받은 바 있었다. 가족력 상에는 특별한 이상이 없었다. 신체검진상 전신의 만성 습진성 피부병변, 크고 뭉특한 코, 아구창 등을 관찰할 수 있었고, 청진상의 양폐야의 부잡음 및 우측 하엽의 호흡음이 감소되었다. 전신 흉부방사선 촬영상 양측 폐야의 기관지확장성 변화를 동반한 우하엽의 흉수 및 경화가 관찰되었으며, 말초혈액검사상 호산구수치($750/{\mu}L$) 및 면역글로불린 E 수치(5,001 U/mL)가 증가되었다. 환아는 임상적으로 고 IgE 증후군이 의심되었으며, 유전자 검사를 통해 확진하였다(Arg382Trp). 최근의 연구에 따르면, 고 IgE 증후군의 주된 원인으로 STAT3 유전자의 이상이 알려져 있으며, 이를 유발하는 여러 돌연변이가 보고되어 있다. 저자들은 STAT3 유전자의 돌연변이 중 잘 알려진 Arg382Trp 돌연변이를 우리나라에서 최초로 유전자 검사를 통해 본 환아에게서 확진하였기에 문헌고찰과 함께 보고하는 바이다. 고 IgE 증후군은 만성 습진성 피부병변, 반복적인 호흡기 감염 등 특징적인 병력이 있는 환자에서 고 IgE 혈증이 동반될 때 임상적으로 의심할 수 있으며, 유전학 검사로 확진이 가능하다.

• 한국식품영양과학회지
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• 제45권4호
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• pp.533-541
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• 2016

페놀화합물의 함량이 높다고 알려진 카카오(powder)로부터 카카오 추출물(CE)을 획득한 후, CE가 pancreatic lipase의 활성에 미치는 영향과 CE를 함유한 emulsion의 aging에 의한 가수분해율 변화를 살펴보기 위하여 두 가지 형태의 기질을 사용한 pH-stat digestion model을 이용하였다. Type I 의 경우 소화액에 CE와 콩기름을 첨가하여 emulsion을 제조하였으며 aging time(0, 5, 24시간)에 따른 가수분해 변화를 살펴보았다. CE를 첨가하였을 때의 가수분해율은 CE를 첨가하지 않았을 때와 큰 차이를 보이지 않아 CE가 pancreatic lipase 활성에 영향을 주지 않았다고 판단된다. 그러나 aging time이 지남에 따라 CE를 첨가하였을 때와 CE를 첨가하지 않았을 때의 가수분해율 모두 감소하였다. 이는 CE의 영향보다는 aging time이 길어짐에 따라 emulsion의 안정도가 낮아져 지방구 크기가 증가하여 가수분해율이 모두 감소한 것으로 생각되고, 따라서 이 모델에서는 CE에 의한 가수분해 저하가 크지 않았다. 한편 type II의 경우 먼저 콩기름과 CE, Tween 20를 혼합하고 고압균질기를 사용하여 micro-emulsion을 제조한 후, 이를 기질로 하여 aging time(0, 2, 4, 7, 18, 43일)에 따른 가수분해율 변화를 살펴보았다. 그 결과 aging time에 따라 CE를 첨가하지 않은 control과 CE를 첨가한 CE-emulsion의 가수분해율이 감소하였는데, 특히 control보다 CE-emulsion이 더 많이 감소하여 43일에는 control의 ${\Phi}$ max가 92.13%(0일, 96.53%)였으나 CE-emulsion은 77.69%(0일, 97.91%)를 보이면서 CE-emulsion의 가수분해 반응이 control에 비해 낮았다. 다른 kinetic parameter(k value, $t_{1/2}$ 등)에서도 이와 유사한 경향을 나타냈다.

• 동의생리병리학회지
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• 제23권3호
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• pp.554-561
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• 2009

Soyangin-Hyeongbangpaedok-san(SHBPDS) is a herbal formula used for the common cold or upper respiratory illness. In order to investigate the effect of SHBPDS, mice were orally administered with SHBPDS alcohol extract for 7 days followed by intravenous anti-CD3 injection. In addition, splenocytes and CD4 T cells were cultured with SHBPDS in response to anti-CD3 in vitro and cytokines and transcription factors were evaluated. In vivo treatment with SHBPDS significantly augmented the expressions of the percentage of CD4 T cells and CD 69, an indicator of early T cell activation. Serum levels of IL-4 were significantly increased but those of IFN-${\gamma}$ and IL-2 did not reach statistical significance. The expressions of IFN-${\gamma}$ and T-bet mRNA were significantly downregulated in SHBPDS treated mice while those of IL-4 and C-Maf were significantly upregulated. In vitro stimulation of splenocytes and CD4 T cells by SHBPDS resulted in a reduction in IFN-${\gamma}$ secretion and STAT4 activity. The IL-4 releases from both cells were slightly reduced, but STAT6 activity was rather increased. In conclusion, SHBPDS exerted an inhibition in the expression of IFN-${\gamma}$, T-bet and STAT4 while IL-4, C-Maf and STAT6 were increased. Further studies are required to examine its pharmacological effects using more appropriate animal experiments.

• BMB Reports
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• 제33권6호
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• pp.454-462
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• 2000

Interleukin-4(IL-4) is known to be a major cytokine regulating immunoglobulin E(IgE) response by the induction of IgE production and type II IgE receptor(IgER II: CD23) expression. Recently, however, the role of neuroendocrine factors has been implicated in modulating the IgE response. Among various neuroendocrine growth factors, we investigated the effects of the insulin-like growth factor-1(IGF-1) since IL-4 and IGF-1 share common intracellular signaling molecules, such as the insulin receptor substrate-1/2(IRS-1/2) to induce a specific cellular response. In the human peripheral blood mononuclear cell (PBMC) cultures, IGF-1 was capable of inducing a substantial level of IgE production in a dose-dependent manner. It also noticeably upregulated the IL-4-induced or IL-4 plus anti-CD40-induced IgE production. Similarly, the IGF-1-induced IgE production was enhanced by IL-4 or anti-CD40 in an additive manner, which became saturated at high concentrations of IGF-1. Although IGF-1 alone did not induce IgER II (CD23) expression, it augmented the IL-4-induced surface CD23 expression in a manner similar to the action of anti-CD40. These results imply that IGF-1 is likely to utilize common signaling pathways with IL-4 and anti-CD40 to induce IgE and IgER II expression. In support of this notion, we observed that IGF-1 enhanced the IL-4-induced signal transducers and activators of transcription 6(STAT6) activation and independently induced $NF-{\kappa}B$ activation. Both of these bind to the IgE(C) or IgER II (CD23) promoters. Together, our data suggest that IL-4 and IGF-1 work cooperatively to activate STAT6 and $NF-{\kappa}B$. This leads to the subsequent binding of these transcription factors to the $C{\varepsilon}$ and CD23 promoters to enhance the expression of IgE and IgER II. The observed differential ability of IGF-1 on the induction of IgE vs. IgER II is discussed based on the different structure of the two promoters.

• 한국식품영양과학회지
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• 제41권9호
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• pp.1226-1234
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• 2012

본 연구에서는 염증반응을 조절하는 다양한 신호전달체계를 중심으로 분자생물학적 방법을 통해 piceatannol의 항염증 기전을 규명하였다. LPS로 염증반응을 유도한 Raw 264.7 대식세포에서 piceatannol은 iNOS의 발현 억제를 통해 NO의 생성을 감소시키고 염증성 사이토카인(TNF-${\alpha}$, IL-6, IL-$1{\beta}$)의 생성을 감소시켰다. 염증반응을 조절하는 신호전달체계 중 piceatannol은 LPS에 의해 유도된 $I{\kappa}B$의 분해와 p65의 핵으로의 이동을 억제하고, LPS에 의해 유도된 SAPK/JNK의 인산화를 억제하였다. 또한 piceatannol은 LPS와 IL-6(LPS에 의해 증가됨)에 의한 STAT3의 활성화를 억제하였다. 뿐만 아니라 piceatannol은 Nrf2의 핵 내 축적을 야기하고 ARE의 transcriptional activity를 증가시켜 HO-1의 발현을 증가시켰다. 본 연구의 결과, piceatannol은 NF-${\kappa}B$와 AP-1, STAT3 신호전달의 억제를 통해, 그리고 HO-1의 발현 증가를 통해 항염증 효과를 나타내었다(Fig. 8).

• 대한한방내과학회지
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• 제26권1호
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• pp.74-92
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• 2005

Objectives/Methods : To analyze the effect of Injinchunggantang(IJCGT) to Interferon-${\alpha}/{\beta}$ signal transmission system in HepG2 cells, HepG2 Cell were treated with IJCGT. Also, revelation of MxA, 2'5'-OAS mRNA leaded by Interferon-${\alpha}/{\beta}$ and revelation and activation of Jak1, TYK1, and STAT 1, all main signal transmission factors, were analyzed. Results : The analysis resulted in the following 1. With interferon ${\alpha}/{\beta}$ there was no affect cell propagation of Hep G2 cells. With IJCGT alone, cell propagation of HepG2 was promoted, and cell propagation control function was recovered. 2. With interferon ${\alpha}/{\beta}$ cell death was unaffected. With IJCGT apoptosis of HepG2 cell was restrained, and the cell's reaction to interferon was unaffected. 3. With interferon ${\alpha}/{\beta}$ treatment mRNA revelation of MxA and 2'5'-OAS was induced. When HepG2 cells were injected with IJCGT without interferon ${\alpha}/{\beta}$ treatment, mRNA revelation of MxA and 2'5'-OAS increased in proportion to the treatment density. With pre-treatment of IJCGT, leaded with interferon ${\alpha}/{\beta}$, promoted revelation of MxA, 2'5' -OAS mRNA. 4. Though mRNA revelation of lakl, TYK1 and STAT1 was unaffected with IJCGT, activation of STAT1 was promoted with an increase of phosphorylation of STAT1 protein. With pre-treatment of IJCGT, Jak1, TYK2, STAT1 phosphorylation, leaded with interferon, strengthened. 5. TNF-a, IL-1b and LPS present, revelation of MxA and 2'5'-OAS mRNA leaded by interferon was restrained when HepG2 cells were treated with IJCGT, and the interferon signal transmission system restraint action leaded by inflammatory cytokines was moderated. Conclusion : These results support a role for IJGCT in promotion of anti-virus action through maintainance of the liver's sensibility toward interferon. A clinical study of an interferon treated patient treated also with IJGCT is needed to determine its efficacy.

• KSBB Journal
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• 제15권2호
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• pp.134-138
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• 2000

알콜증류폐액에 빵효모를 배양하는 중에 glucose와 ammo-nium을 자동첨가함으로써 폐액배양액의 균체농도를 높여서 알콜증류폐액의 이용성을 증가시키고자 하였다. 배양중에 glucose를 공급하여 줌으로서 공급하지 않은 경우보다 1.3배 더 높은 균체농도를 얻었으며, glucose와 (NH4)2SO4를 공급하여 줌으로써 5.8배 더 높은 균체농도를 얻었다. Glucose의 경우에는 배양액의 DO를 제어파라미터로 하는 제어방법을 사용하여 자동첨가하고, ammonium의 경우에는 pH조정제로서 NH4OH을 사용함으로서 pH제어기에 의하여 자동으로 공급되도록 배양하였다. 배양결과 증식의 정체없이 배양 22.5시간후에 최대 12.0 g/L의 건조균체량에 도달하였으며, 균의 최대비증식속도는 0.18 hr-1였고, 대당균체수율이 약 0.54g/gdldjTdmamfh glucose의 첨가가 경제적이라고 생각되었다. 증균배양으로 폐액배양액의 COD를 약 22% 더 감소시킬 수 있었다.

• Bulletin of the Korean Chemical Society
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• 제31권4호
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• pp.921-924
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• 2010

Blocking of IL-6 has been postulated to be an effective therapy in the pathogenesis of several inflammatory diseases. The current study was performed to examine the potential effects of alkamides isolated from P. longum and P. nigrum on IL-6 induced Stat3 activation and identify the structure-activity relationship of these alkamides in human hepatoma cells. Among 10 alkamides isolated from P. longum and P. nigrum, compounds 6, 7 and 9 were identified as strong inhibitors of IL-6 action, which inhibit IL-6 induced Stat3-dependent luciferase activities. These inhibitory activities were positively influenced by the presence of piperidine moiety.