• Natural Product Sciences
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• 제15권1호
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• pp.1-7
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• 2009

This study was performed to investigate the cell growth inhibitory effect of tissue cultured root of wild Panax ginseng C.A. Mayer (tcwPG). The human stomach carcinoma cell line, MKN 74, was incubated with 70% EtOH extract of tcwPG or Panax ginseng C.A. Mayer (PG) for 24 hrs. tcwPG inhibited cell growth at a concentration of $250{\mu}g/ml$. However, Panax ginseng extract did not inhibit cell growth at the same concentration. We also tested the ethyl acetate and $H_2O$ fractions of tcwPG. The inhibitory effect of the ethyl acetate fraction on cell proliferation in MKN 74 cells was more potent than that of the crude extract, and the inhibitory effect of the $H_2O$ fraction was less than that of the ethyl acetate fraction. When we separated tcwPG into polar and non-polar saponin fractions and then measured cell growth inhibition, the non-polar saponin in tcwPG exhibited cytotoxicity. To compare the effects of tcwPG on various cancer cell lines, we measured cytotoxicity in MKN 74 (stomach cancer cell line), SW 620 (colon cancer cell line) and PC 3 (prostate cancer cell line). All three cell lines showed cell growth inhibition, and the cell growth inhibitory effects were not quite different in the various cell lines. The non-polar saponins of tcwPG arrested PC 3 cells at G1-phase as did Panax ginseng.

• Natural Product Sciences
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• 제12권1호
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• pp.38-43
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• 2006

Ilekudinol B is one of the flavonoids isolated from Weigela subsessilis (Caprifoliaceae). In the present study, the suppression effect of ilekudinol B on tumor necrosis factor $(TNF)-{\alpha}-induced$ cyclooxygenase-2 (COX-2) expression was investigated in human colon epithelial cell line HT-29. Interleukin-8 (IL-8) production and prostaglandin $E_2\;(PGE_2)$ secretion was measured by enzyme-linked immunosorbent assay (ELISA). COX-2 and nuclear factor $(NF)-{\kappa}B$ expression were determined by Western blot analysis. Ilekudinol B significantly inhibited $TNF-{\alpha}-induced$ secretion of IL-8 and prostaglandin $E_2\;(PGE_2)$ from the human colon epithelial cell line HT-29 in a concentration-dependent manner. In addition, ilekudinol B remarkably diminished $TNF-{\alpha}-induced$ COX-2 expression and $NF-{\kappa}B$ p65 subunit translocation to the nucleus. In conclusion, our results indicate that ilekudinol B may have anti-inflammatory activity on $TNF-{\alpha}-dependent$ colonic inflammation.

• Journal of Nutrition and Health
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• 제36권3호
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• pp.270-279
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• 2003

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid (LA) and exhibits anticarcinogenic activity in a variety of animal models. We have previously observed that CLA inhibited the growth of Caco-2 cells, a human colon adenocarcinoma cell line. The present study was performed to determine whether the growth inhibitory effect of CLA is related to change in secretion of IGF- II and/or IGF-binding proteins (IGFBPs) that have been shown to regulate Caco-2 cell proliferation by an autocrine mechanism. Cells were incubated in serum-free medium with various concentrations of CLA or linoleic acid (LA). Immunoblot analysis of 24-hours, serum-free, conditioned medium using a monoclonal anti-IGF-IIantibody revealed that Caco-2 cells secreted both mature 6,500 Mr and higher Mr forms of pro IGF-II. The levels of pro IGF-II and mature IGF-IIwere decreased by 43 $\pm$ 2% and 53 $\pm$ 6%, respectively by treatment with 50 $\mu$ M CLA. LA slightly increased pro IGF- II levels. Results from Northern blot analysis showed that CLA decreased IGF-II mRNA levels at 50 $\mu$ M concentration suggesting that CLA regulation of IGF-II protein expression occurs partly at the transcriptional level. Ligand blot analysis of conditioned media using 1251-IGF-II revealed that CLA slightly decreased IGFBP-2 levels and increased IGFBP-4 levels. We confirmed our previous results that CLA inhibited cell growth in a dose-dependent manner but LA slightly increased cell growth. Exogenous IGF-II mitigated the growth inhibitory effect of CLA. These results indicate that the growth inhibitory effect of CLA may be at least in part mediated by decreasing IGF-II and IGFBP-2 secretion and increasing IGFBP-4 secretion in Caco-2 cells.

• 한국식품영양과학회지
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• 제41권8호
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• pp.1100-1105
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• 2012

본 실험에서는 녹차추출물이 항암화학요법제의 항암작용 증강제로서의 이용가능성을 추정하기 위하여 광범위 항암화학요법제인 시스플라틴의 항암작용에 미치는 녹차추출물의 영향을 생쥐 대장암세포를 이용하여 관찰한 결과, 생쥐대장암세포인 CT26 세포를 배양하여 녹차추출물이나 EGCG을 투여하면 시스플라틴에 의한 세포독성이 증가되었는데, 시스플라틴의 세포독성에 미치는 EGCG와 녹차추출물의 효과 차이는 없었다. 생쥐에 CT26 세포를 주사하여 유발된 종양의 성장이 시스플라틴군보다 시스플라틴+녹차추출물 병합 투여로 현저히 감소되었다. 이상의 결과 녹차추출물은 화학요법제인 시스플라틴과 병합 투여할 경우 화학요법제 단독 투여 시보다 대장암 세포의 활성도 감소가 더 크고, 생쥐대장암의 크기를 감소시키는 작용도 더 크기 때문에 녹차추출물을 화학요법제와 병행투여하면 항암치료 효과가 증가될 것으로 생각된다. 따라서 녹차추출물은 항암화학요법제에 의한 암치료에서 치료효과를 증강시킬 수 있는 보조제로서 이용될 수 있을 것으로 기대되며, 이러한 효과를 입증하기 위한 더 많은 연구가 있어야 할 것으로 사료된다.

• Applied Biological Chemistry
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• 제49권1호
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• pp.21-24
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• 2006

6종의 인체 암(폐암, 피부암, 결장암, 자궁암, 선암 및 뇌암)과 그의 17가지 세포주들에 대한 리간드 화합물 3,6-bis(2'-pyridyl)pyridazine(1) 과 3,6-bi s(6'-methyl-2'-pyridyl)pyridazine(2) 그리고 그들의 전이금속(Ni(II), Cu(II) 및 Zn(II)) 착 화합물들 $(3{\sim}6)$ 세포독성을 각각 측정하였다. 그 결과, 특히 Cu(II) 착 화합물, bis-[3,6-bis-(6'-methyl-2'-pyridyl)pyridazine-$k^2N^2,N^3$]chlorocopper(II)perchlorate (4)는 뇌암(SNB-19)과 결장암(SW-62) 세포주에 대하여 제1세대 항암제인 Cis-platin보다 높은 세포독성을 나타내었다.

• Nutrition Research and Practice
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• 제13권1호
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• pp.58-63
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• 2019

BACKGROUND/OBJECTIVES: Telomeres are located at the chromosomal ends and progressively shortened during each cell cycle. Telomerase, which is regulated by hTERT and c-MYC, maintains telomeric DNA sequences. Especially, telomerase is active in cancer and stem cells to maintain telomere length for replicative immortality. Recently we reported that walnut phenolic extract (WPE) can reduce cell viability in a colon cancer stem cell (CSC) model. We, therefore, investigated the effect of WPE on telomere maintenance in the same model. MATERIALS AND METHODS: $CD133^+CD44^+$ cells from HCT116, a human colon cancer cell line, were sorted by Fluorescence-activated cell sorting (FACS) and treated with WPE at the concentrations of 0, 10, 20, and $40{\mu}g/mL$ for 6 days. Telomere lengths were assessed by quantitative real-time PCR (qRT-PCR) using telomere specific primers and DNA extracted from the cells, which was further adjusted with single-copy gene and reference DNA ($ddC_t$). Telomerase activity was also measured by qRT-PCR after incubating the PCR mixture with cell protein extracts, which was adjusted with reference DNA ($dC_t$). Transcriptions of hTERT and c-MYC were determined using conventional RT-PCR. RESULTS: Telomere length of WPE-treated cells was significantly decreased in a dose-dependent manner ($5.16{\pm}0.13$ at $0{\mu}g/mL$, $4.79{\pm}0.12$ at $10{\mu}g/mL$, $3.24{\pm}0.08$ at $20{\mu}g/mL$ and $3.99{\pm}0.09$ at $40{\mu}g/mL$; P = 0.0276). Telomerase activities concurrently decreased with telomere length ($1.47{\pm}0.04$, $1.09{\pm}0.01$, $0.76{\pm}0.08$, and $0.88{\pm}0.06$; P = 0.0067). There was a positive correlation between telomere length and telomerase activity (r = 0.9090; P < 0.0001). Transcriptions of both hTERT and c-MYC were also significantly decreased in the same manner. CONCLUSION: In the present cell culture model, WPE reduced telomere maintenance, which may provide a mechanistic link to the effect of walnuts on the viability of colon CSCs.

• 생명과학회지
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• 제27권10호
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• pp.1215-1224
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• 2017

현재까지 다양한 암의 발병 원인이 밝혀졌는데, 그 중 하나로써 DNA에 돌연변이가 축적되어 유전체가 불안정 해짐에 따라 암이 발생될 수 있는 기작들이 주목받고 있다. 생물정보학과 유전체학의 발달에 따라 질병 연구에 있어서 보다 더 정확하고 신뢰성 있는 바이오마커를 찾는 것이 가능해졌다. 따라서, 생물정보학과 유전체학의 연구 기반을 바탕으로 한 암의 바이오마커는 암의 조기진단뿐만 아니라, 더 나아가 암 발생 예측과 암환자의 예후 진단에 적용될 수 있다. 최근 들어 인간 유전체에서 약 45%를 차지하는 이동성 유전인자(transposable elements, TEs)가 유전자의 발현 조절과 DNA의 돌연변이를 유도함으로써 다양한 질병에 영향을 미친다는 사실이 밝혀짐에 따라, 이러한 이동성 유전인자들이 암의 발생과 어떤 연관이 있는지에 대한 연구 또한 활발히 진행되고 있다. 따라서 우리는 이동성 유전인자가 대장암과 어떤 연관성이 있는지에 대해 조사를 하였으며, 이를 어떻게 바이오마커로 활용할 수 있는지 알아보았다. 우선, 이동성 유전인자 중 인간 유전체에 많이 존재하면서 유전체에 많은 영향을 미치는 LINE-1 (long interspersed nuclear element-1, L1)과 Alu, LTR (long terminal repeat) 위주로 확인하였다. 흥미롭게도, 대장암 세포에서 LINE-1의 저메틸화, APC 유전자 내에 LINE-1 삽입, Alu의 저메틸화와 과메틸화, LTR 삽입에 따른 isoform 발생 등이 특징적으로 나타나는 것을 알 수 있었다. 또한 원발암유전자에서의 L1 저메틸화가 대장암 전이의 바이오마커로 쓰일 수 있다는 것과 Alu에 의한 MLH1 돌연변이가 가족성 및 유전성 대장암에서 흔히 발견된다는 것을 알 수 있었다. 이 때 이동성 유전인자에 의하여 영향 받는 유전자들의 발현을 in silico 발현 분석을 통하여 분석하였으며, 조직별, 성별 특이적 발현 양상을 제시하였다. 이들을 토대로 대장암 바이오마커를 개발하여 유전성 대장암의 예측 및 대장암 진단 또는 대장암 예후 예측을 통한 개인 맞춤형 치료에 활용할 수 있을 것으로 예상된다.

• KSBB Journal
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• 제8권5호
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• pp.473-477
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• 1993

하이브리도마 배양을 위해 첨가한 기존의 혈 청농도는 10% FBS였으나, 이 농도는 3%까지 줄여도 세포의 비성장속도와 최고세포농도에 차이가 없었다. 세포성장을 촉진한다고 알려진 물 질들을 1% FBS 배지에 첨가하였을 때 insulin, pyruvate, oxaloacetate, pluronic F-68 등에 의해 세포성장이 촉진되었다. 3% FBS는 2% CS로 대치할 수 있었고, 혈청의 농도는 IPOP의 첨가시 0.5 % CS에서도 active proliferation을 보였다. 최종 조성의 배지가격은 기존의 10 % FBS 배지의 1/10 정도였으며 배지조성을 cell line에 따라 달리 결정함으로써 배지의 가격은 현저히 낮출 수 있음을 알았다.

• 동의생리병리학회지
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• 제22권2호
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• pp.282-289
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• 2008

We evaluated the effect of SHBCS on adhesion and invasion of colon L5-26 adenocarcinoma cell line in vitro in vitro and experimental liver metastasis in vivo. SHBCS showed little inhibitory effect on colon 26-L5 cell proliferation. At the concentration of up to 500 mg/ml of SHBCS 80% of cells were viable. SHBCS showed no inhibitory effect on adhesion and invasion of colon 26-L5 cells, which were placed on matrigel. In a dose dependent manner, oral administration of SHBCS showed a significantly inhibitory effect on liver metastasis from colon 26-L5 injected mice. When mice were depleted of NK cells or macrophages before tumor inoculation, SHBCS significantly decreased liver metastasis fromf the tumor injected mice. Compared with the control mice, SHBCS increased the populations of macrophages and NK cells by 30%, 18%(10 mg/mouse, 50 mg/mouse) and 5%, 1% (10 mg/mouse, 50 mg/mouse) respectively. Compared with the control mice, SHBCS increased the populations of CD4 cells by 5%, 18% (10 mg/mouse, 50 mg/mouse) respectively. Spelenocytes from mice administerd with SHBCS were stimulated with LPS plus ConA, proliferation of splenocytes from mice administerd with SHBCS was 140%, 146%(10 mg/mouse, 50 mg/mouse) compared with th control mice. In conclusion, the present study suggests that SHBCS may have an inhibitory effect on liver metastasis through immunopotentiating activity which is associated with macrophages and NK cells.

• IMMUNE NETWORK
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• 제4권1호
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• pp.31-37
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• 2004

Background: 1-8D gene is a member of human 1-8 interferon inducible gene family and is shown to be overexpressed in fresh colon cancer tissues. Three peptides 1-6, 3-5 and 3-7 derived from 1-8D gene were shown to have immunogenicity against colon cancer. Methods: To study tumor immunotherapy of these peptides we established an adoptive transfer model. $D^{b-/-}{\times}{\beta}2$ microglobulin (${\beta}2m$) null mice transgenic for a chimeric HLA-A2.1/$D^b-{\beta}2m$ single chain (HHD mice) were immunized with irradiated peptide-loaded RMA-S/HHD/B7.1 transfectants. Spleens were removed after last immunization, and splenocytes were re-stimulated in vitro. Lymphocytes from vaccinated HHD mice were transferred together with IL-2 to the tumor bearing nude mice that were challenged S.C. with the HCT/HHD/B7 colon carcinoma cell line that was found to grow in these mice. Results: Peptide 3-5 was found to be highly effective in CTL activity. Adoptively transferred anti-peptide 3-5 cytolytic T lymphocytes caused significant retardation in tumor growth. Conclusion: This study shows that peptide 3-5 can be the most effective candidate for the vaccine of adoptive immunotherapy against colon cancer.