• 한국식품저장유통학회지
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• 제17권5호
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• pp.752-756
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• 2010

나비류 추출물은 전통적으로 다양한 활성을 보유하여 의약용으로 사용되어졌다. 5종의 나비(산제비나비[Papilio maackii], 호랑나비[Papilio xuthus], 배추흰나비[Pieris rapae], 남방호랑나비[Eurema hecabe], 왕오색나비[Sasakia charonda])를 이용하여 물, dimethly sulfoxide (DMSO), ehtanol 및 methanol로 추출한 추출물로 항산화 활성 및 Cox-2 promoter assay를 수행하였다. 그 결과 산제비나비의 추출물이 전반적으로 높은 항산화활성을 나타내었으며, Cox-2 promoter assay에서는 호랑나비의 DMSO 분획이 가장 저해활성이 높은 것으로 나타났다. 활성이 높은 추출물을 대상으로 분리 및 정제를 통하여 유용한 식의약 소재로의 기초연구가 더 필요하다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4453-4458
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• 2012

Angiogenesis plays a significant role in colorectal cancer (CRC) and cyclooxygenase-2 (COX-2) appears to be involved with multiple aspects of CRC angiogenesis. Our aim was to investigate the inhibitory effects of Tan II-A (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of expression of COX-2 and VEGF in CRC. We established the mice xenograft model of C26 CRC cell line, and injected 0.5, 1, 2mg/kg of Tan II-A and 1mg/kg of 5-FU in respectively in vivo. Then, we assayed tumor weight and volume, and evaluated microvascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids were transfected into HCT-116 cells, followed by detection of COX-2 promoter activity by chemiluminescence, and detection of COX-2 mRNA expression by fluorescence quantitative PCR. Taken together, the results showed Tan II-A could inhibit tumor growth and suppress the VEGF level in vivo. HCT-116 cell experiments showed marked inhibitory effects of Tan II-A on COX-2 and VEGF in a dose-dependent manner. The results indicate that Tan II-A can effectively inhibit tumor growth and angiogenesis of human colorectal cancer via inhibiting the expression level of COX-2 and VEGF.

• 생명과학회지
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• 제27권9호
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• pp.1020-1030
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• 2017

대장암은 미국 등 서양 국가뿐만 아니라 국내에서도 2번째로 많이 발병이 되는 암으로 알려져 있다. 역학조사에 의하면 오메가-3를 많이 섭취한 인종에서 대장암 발생빈도가 감소하고 최근 오메가-3는 수종의 암에 대해 항암작용을 나타낸다고 한다. 이에 본 연구에서는 대장암에서 DHA의 항침윤, 항혈관 신생 및 항종양 형성능 억제의 기전을 규명하여 다음과 같은 결과를 얻었다. DHA는 인체 대장암 세포주 HT29 의 증식을 농도 의존적으로 억제하였으나 AA는 거의 영향이 없었다. FACS 분석에서 DHA 처리했을 때 Sub G1 phase의 세포가 DHA의 농도 의존적으로 증가 하였다. DHA 처리 후 cleaved PARP가 증가하고, uncelaved caspase-3가 감소 하였다. HT29 세포의 침윤능은 DHA 처리에 의해 억제 되었다. DHA 처리 후 MMP-9 및 MMP-2 mRNA양이 감소 되었을 뿐만 아니라 그 promoter의 reporter 활성도 억제하였으며 VEGF promoter 활성도 DHA에 의해 억제 되었다. NF-kB promoter 활성 및 핵으로의 이동도 DHA에 의해 억제 되었다. In vivo 동물실험에서 생쥐 대장암 세포주인 MCA38에 대한 Fat-1 transgenic mice에서의 종양 형성능은 현저히 억제 되었다. 면역형광염색법을 이용한 Fat-1 transgenic mice의 종양 조직에서의 TUNEL 양성세포는 wild type mice에 비해 현저히 증가하였으나 CD31의 형광강도는 감소 되었다. 이상의 결과로 오메가-3는 대장암 세포에서 NF-kB 억제에 따른 COX-2, MMP-2 및 MMP-9 등 matrix matalloproteinase의 억제를 통한 침윤능의 억제, VEGF 억제를 통한 혈관신생의 억제등 복합적 기전에 의해 항암작용을 나타내리라 생각되며, 따라서 오메가-3는 대장암의 예방 및 치료에 유용하게 사용될 수 있으리라 생각된다.

• 한국식품저장유통학회지
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• 제13권4호
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• pp.513-518
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• 2006

최근 곤충자원은 약용 및 식용으로 활용하려고 많은 연구가 되고 있으며 미래의 자원으로 발전할 수 있는 가능성은 충분하다. 본 연구는 곤충자원 중 칠성무당벌레와 무당벌레를 이용하여 생물학적 활성과 함께 약용 및 식용으로의 활용가능성을 알아보고자 하였다. 생물학적 활성을 알아보기 위하여 이들 추출물을 이용하여 항산화관련 실험인 DPPH, FRAP, linoleic acid 산화 억제실험을 하였으며, 분자 염증에 관련된 유전자인 Cyclooxygenase-2(Cox-2)의 promoter의 유전자 발현의 억제 유무를 알아보았다. 항산화 효과에 있어서는 무당벌레의 DW추출물에서 높은 활성을 나타내었으며, Cox-2의 promoter 활성을 조사한 결과 DW 추출물에서 Cox-2의 promoter 활성을 약 25% 정도 억제하는 무당벌레의 DW추출물을 발견하였는데 추출물의 산업적인 활용가능성을 확인하기 위하여 보다 많은 연구가 필요하다.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2006년도 한국약용작물학회 공동춘계학술발표회
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• pp.472-473
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• 2006

• Journal of Ginseng Research
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• 제35권2호
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• pp.200-208
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• 2011

Ginsenoside (G) $Rp_1$ is a ginseng saponin derivative with anti-cancer and anti-inflammatory activities. In this study, we examined the mechanism by which G-$Rp_1$ inhibits inflammatory responses of cells. We did this using a strategy in which DNA constructs containing cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) promoters were transfected into HEK293 cells. G-$Rp_1$ strongly inhibited the promoter activities of COX-2 and iNOS; it also inhibited lipopolysaccharide induced upregulation of COX-2 and iNOS mRNA levels in RAW264.7 cells. In HEK293 cells G-$Rp_1$ did not suppress TANK binding kinase 1-, Toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-${\beta}$ (TRIF)-, TRIF-related adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-${\kappa}$B by the myeloid differentiation primary response gene (MyD88)-induced. However, G-$Rp_1$ strongly suppressed NF-${\kappa}$B activation induced by I${\kappa}$B kinase (IKK)${\beta}$ in HEK293 cells. Consistent with these results, G-$Rp_1$ substantially inhibited IKK${\beta}$-induced phosphorylation of $I{\kappa}B{\alpha}$ and p65. These results suggest that G-$Rp_1$ is a novel anti-inflammatory ginsenoside analog that can be used to treat IKK${\beta}$/NF-${\kappa}$B-mediated inflammatory diseases.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2007년도 제48회 학술심포지움 및 추계국제학술대회
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• pp.85.2-85.2
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• 2007

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• 생명과학회지
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• 제16권4호
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• pp.691-698
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• 2006

본 연구에서 최근 세포내 신호전달을 매개하는 중요한 효소로써 PLD 동위효소에 대하여, $CoCl_2$가 PLD 동위효소의 활성을 증가시킨다는 사실을 밝혔으며, 중간에 매개되는 단백질로써, PLD1은 p38 MAP kinase, PKA와 $PKC-{\delta}$의 조절을 받고 PLD2는 p38 MAP kinase와 PLC의 조절을 받으므로 그 활성 기전이 각각 다르다는 사실을 확인하였다. 그리고 $CoCl_2$에 의해 생성되는 활성산소 종에 의한 염증상태가 유도될 것이라고 예상하였고 $CoCl_2$가 PLD 동위효소를 매개로 하여 염증상태에서만 특이적으로 발현되고 염증반응을 매개하는 COX-2 단백질에 어떠한 영향을 미칠 것인가를 조사하였다. 결과적으로 $CoCl_2$에 의해 PLD 효소 활성이 증가됨으로써 COX-2의 발현이 증가한다는 것을 발견하였을 뿐만 아니라 COX-2의 발현에 대하여 COX-2 promoter의 활성도 증가한다는 사실을 확인함으로써 전사수준에서의 결과도 이를 뒷받침 해 주고 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4989-4994
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• 2014

Background: It has been reported that COX-2 expression is associated with MMP-2 expression in thyroid and breast cancers, suggesting that MMPs are linked to COX-2-mediated carcinogenesis. Several polymorphisms within the MMP2 promoter region have been reported in cases with oncogenesis and tumor progression, especially in colorectal carcinogenesis. Materials and Methods: This research evaluated risk of association of the SNPs, including genes for COX-2 (AIG transition at +202) and MMP-2 (Crr transition at-1306), with colorectal cancer in 125 patients and 125 healthy controls. Results and Conclusions: Our data confirmed that MMP2 C-1306 T mutations were significantly more common in colon cancer patients than in our control Saudi population; p=O.0121. On the other hand in our study, there was no significant association between genotype distribution ofthe COX2 polymorphism and colorectal cancer; p=0.847. An elevated frequency ofthe mutated genotype in the control group as compared to the patients subjects indeed suggested that this polymorphism could decrease risk in the Saudi population. Our study confirmed that the polymorphisms that could affect the expressions of MMP-2 and COX-2 the colon cancer patients were significantly higher than that in the COX-2 negative group. The frequency of individuals with MMP2 polymorphisms in colon cancer patients was higher than individuals with combination of COX2 and MMP2 polymorphisms. Our study confirmed that individuals who carried the polymorphisms that could affect the expressions ofCOX2 are more susceptible to colon cancer. MMP2 regulatory polymorphisms could be considered as protective; further studies need to confirm the results with more samples and healthy subjects.

• IMMUNE NETWORK
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• 제3권3호
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• pp.201-210
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• 2003

Objective: The role of prostaglandin $E_2$ (PGE2) in the etiopathogenesis of immune and inflammatory diseases has become the subject of recent debate. To determine the role of PGE2 in rheumatoid arthritis (RA), we tested the effect of exogenous PGE2 on the production of cyclooxygenase-2 (COX-2) by rheumatoid synoviocytes. Methods: Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and cultured in the presence of PGE2. The COX-2 mRNA and protein expression levels were determined by RT-PCR and Western blot analysis, respectively. The PGE2 receptor subtypes in the FLS were analyzed by RT-PCR. Electrophoretic mobility shift assay (EMSA) was used to measure the NF-${\kappa}B$ binding activity for COX-2 transcription. The in vivoeffect of PGE2 on the development of arthritis was also tested in collagen induced arthritis (CIA) animals. Results: PGE2 ($10^{-11}$ to $10^{-5}M$) dose-dependently inhibited the expression of COX-2 mRNA and the COX-2 protein stimulated with IL-$1{\beta}$, but not COX-1 mRNA. NS-398, a selective COX-2 inhibitor, displayed an additive effect on PGE2-induced COX-2 downregulation. The FLS predominantly expressed the PGE2 receptor (EP) 2 and EP4, which mediated the COX-2 suppression by PGE2. Treatment with anti-IL-10 monoclonal antibodies partially reversed the PGE2-induced suppression of COX-2 mRNA, suggesting that IL-10 may be involved in modulating COX-2 by PGE2. Experiments using an inducer and an inhibitor of cyclic AMP (cAMP) suggest that cAMP is the major intracellular signal that mediates the regulatory effect of PGE2 on COX-2 expression. EMSA revealed that PGE2 inhibited the binding of NF-${\kappa}B$ in the COX-2 promoter via a cAMP dependent pathway. In addition, a subcutaneous injection of PGE2 twice daily for 2 weeks significantly reduced the incidence and severity of CIA as well as the production of IgG antibodies to type II collagen. Conclusion: Our data suggest that overproduced PGE2 in the RA joints may function as an autocrine regulator of its own synthesis by inhibiting COX-2 production and may, in part, play an anti-inflammatory role in the arthritic joints.