• 동의생리병리학회지
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• 제20권3호
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• pp.690-696
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• 2006

Houttuynia cordata Thunb, well known as 'E-Sung-Cho' in Korea, is a traditional medicinal plant generally used in Oriental medicine therapy. In the present study, we investigated the effect of water extract of H. cordafa (WEHC) on the growth of human breast carcinoma MCF-7 cells. Exposure of MCF-7 cells to WEHC resulted in growth inhibition and apoptosis in a dose-dependent manner as measured by MTT assay and fluorescent microscope. The anti-proliferative effect of WEHC was associated with a dose-dependent up-regulation of cyclin-dependent kinase inhibitor p21 in a p53-independent fashion. We found WEHC decreased the levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthease (iNOS) expression without significant changes in the expression of COX-1 , which was correlated with a decrease in prostaglandin $E_2{\;}(PGE_2)$ synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. cordata.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.82-82
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• 1995

4-lBB molecule is expressed on the surface of activated CD4$\^$+/ and CD8$\^$+/ T cells. We generated a panel of anti-4-1 B5 murine mAbs using a fusion protein consisting of the extracellular domain of human 4-1 BB fused to Glutathione S-transferase. The binding activity against cell surface 4-1 BB molecule was assessed by flow cytometry analysis. These studies showed that several anti-4-1 BB mAbs bound to 10-30% of CD4$\^$+/ and CD8$\^$+/T cells in PHA or Con A stimulated PBLs, although these mAbs interacted with only, l-2% of CD4$\^$+/ and CD8$\^$+/ T cells in normal PBLs, indicating the specificity of mAbs to the 4-l BB molecule on activated CD4$\^$+/ and CD8$\^$+/ T cells. Next, we examined the effect of an anti-4-l BB mAb (4B4-1-1) on allogeneic mixed lymphocyte reactions (MLRs). The data indicated that the antibody significantly inhibited the proliferative response at higher concentrations. When tested with several T cell mitogens, the antibody had no stimulatory or inhibitory effects on the mitogen-mediated T cell proliferation. These data suggest that 4-1 BB molecule may play a role in the regulation of antigen-mediated immune response.

• Biomolecules & Therapeutics
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• 제24권1호
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• pp.25-32
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• 2016

Lichens have been known to possess multiple biological activities, including anti-proliferative and anti-inflammatory activities. Vascular cell adhesion molecule-1 (VCAM-1) may play a role in the development of atherosclerosis. Hence, VCAM-1 is a possible therapeutic target in the treatment of the inflammatory disease. However, the effect of lobaric acid on VCAM-1 has not yet been investigated and characterized. For this study, we examined the effect of lobaric acid on the inhibition of VCAM-1 in tumor necrosis factor-alpha (TNF-${\alpha}$)-stimulated mouse vascular smooth muscle cells. Western blot and ELISA showed that the increased expression of VCAM-1 by TNF-${\alpha}$ was significantly suppressed by the pre-treatment of lobaric acid ($0.1-10{\mu}g/ml$) for 2 h. Lobaric acid abrogated TNF-${\alpha}$-induced NF-${\kappa}B$ activity through preventing the degradation of $I{\kappa}B$ and phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 mitogen activated protein (MAP) kinase. Lobaric acid also inhibited the expression of TNF-${\alpha}$ receptor 1 (TNF-R1). Overall, our results suggest that lobaric acid inhibited VCAM-1 expression through the inhibition of p38, ERK, JNK and NF-${\kappa}B$ signaling pathways, and downregulation of TNF-R1 expression. Therefore, it is implicated that lobaric acid may suppress inflammation by altering the physiology of the atherosclerotic lesion.

• 대한수의학회지
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• 제52권2호
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• pp.115-124
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• 2012

Colorectal cancer (CRC) is one of the leading causes of cancer death in western countries or in the developed countries. Zinc intake has been associated with decreased risk of CRC. We investigated the effect of zinc on the formation of colonic aberrant crypt foci (ACF) induced by azoxymethane followed by dextran sodium sulfate in mice. Five-week old ICR mice were fed with the different zinc levels (0.01, 0.1, 1 ppm) for 12 weeks. The numbers of ACF were measured in the colonic mucosa. The ACF number of HZn group was significantly low compared with LZn group or MZn group. Cytosolic superoxide dismutase activity was the highest in HZn group, while thiobarbituric acid reactive substance level for lipid peroxidation was the highest in LZn group. There was no difference in number of PCNA-positive proliferative cells among the groups. TUNEL-positive apoptotic cells were increased in HZn group compared with LZn group. The HZn group exhibited a decrease of ${\beta}$-catenin immunostaining areas compared with the LZn or MZn group. These findings indicate that dietary zinc might exert a protecting effect against colon carcinogenesis by inhibiting the development of ACF in the mice.

• 대한두경부종양학회지
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• 제10권2호
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• pp.102-105
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• 1994

The indolent course of most thyroid papillary carcinomas, even the presence of regional lymph node metastasis, make them unique among human malignant head and neck cancers. Age, sex, extracapsular invasion and anaplastic change are known to be correlated with prognosis. The purpose of this study is to clarify the significance of DNA content analysis as a prognostic factor. Twenty five thyroid papillary carcinomas were possible to be examined by flow cytometric analysis using fresh surgical specimens and three nodular hyperplasias and seven follicular adenomas were included as control group. The results were as follows: l) All of twenty five thyroid papillary carcinomas showed diploidy. 2) S-phase fraction was $1.94{\pm}2.77%$ in normal control group and $2.60{\pm}2.66%$ in papillary carcinoma group. The proliferation index was $8.44{\pm}3.89%$ in normal control and $7.70{\pm}3.63%$ in papillary carcinoma group with even low value. 3) Age, sex, extracapsular spread and lymph node metastasis showed no significant difference. In conclusion, low proliferative activity of thyroid papillary carcinomas are thought to be related with good prognosis.

• 생명과학회지
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• 제16권6호
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• pp.1066-1070
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• 2006

Smooth muscle cell (SMC)의 증식은 혈관성장에 의한 질환의 발병기전의 중요한 요소이다. 혈관 손상 후 SMC의 성장조절에 대한 분자적 기작에 대한 연구는 치료제 개발에 있어 중요한 의미를 지닌다. 이에, 본 연구에서는 TNF family인 RANKL가 SMC의 증식을 촉진함을 입증하였다. RANKL는 p21의 발현을 감소시키고 p21의 promoter활성을 저해함으로써 SMC의 성장을 증가시켰다. 또한 ERK와 p38 MAPK의 활성이 RANKL에 의해 증가하였으며, ERK/p38의 저해제는 RANKL에 의해 유도되는 SMC의 성장을 완전히 억제하였다. 이러한 결과는 ERK와 p38 MAPK가 RANKL에 의해 유도되는 SMC의 증식에 중요한 역할을 함을 보여주는 것이다. 즉, RANK-RANKL-ERK/p38이 SMC의 증식을 매개하는 중요 분자이며, 이들 분자는 혈관 질환을 막는 새로운 치료제 개발의 표적분자가 될 수 있음이 입증되었다.

• Clinical and Experimental Reproductive Medicine
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• 제40권2호
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• pp.67-75
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• 2013

Objective: To investigate the effect of peroxisome proliferator activated receptor ${\gamma}$(PPAR${\gamma}$) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis. Methods: Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPAR${\gamma}$ agonist). Results: We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPAR${\gamma}$ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin $E_2$ production in the ESCs of endometriosis. Conclusion: This study suggests that PPAR${\gamma}$ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.

• Preventive Nutrition and Food Science
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• 제16권3호
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• pp.230-235
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• 2011

Roasted and retorted (RR) chestnuts develop green pigment spots on their surface during storage. The purpose of this study was to evaluate the cytotoxicity of the green pigment using RAW 264.7, MOLT-4, KATOIII and HT-29 cells. The pigment scraped from RR chestnuts (GP), whole RR chestnuts with green pigment spots (GC), whole RR chestnuts without green pigment (WC) and roasted and frozen stored chestnuts (FC) were extracted in 10% DMSO. MOLT-4 cells were less resistant to the cytotoxicity of the chestnut extracts than the RAW 264.7 cells. The GP extracts did not show different responses against $H_2O_2$-induced oxidative stress and LPS-induced NO production compared to the other extracts. The chestnut extracts did not have proliferative activity on either of the KATOIII or HT-29 cells (p>0.05). Our results from the comparison of the green pigment produced on the surface of the RR chestnuts to chestnuts that do not develop the green pigment suggest that the pigment may not be harmful in terms of either cytotoxicity towards immune cells or proliferation of gastrointestinal cancer cells.

• Journal of Ginseng Research
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• 제35권1호
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• pp.86-91
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• 2011

Ginsenoside (G)-F1 is an enzymatic metabolite generated from G-Rg1. Although this metabolite has been reported to suppress platelet aggregation and to reduce gap junction-mediated intercellular communication, the modulatory activity of G-F1 on the functional role of skin-derived cells has not yet been elucidated. In this study, we evaluated the regulatory role of G-F1 on the cellular responses of B16 melanoma cells. G-F1 strongly suppressed the proliferation of B16 cells up to 60% at 200 ${\mu}g/mL$, while only diminishing the viability of HEK293 cells up to 30%. Furthermore, G-F1 remarkably induced morphological change and clustering of B16 melanoma cells. The melanin production of B16 cells was also significantly blocked by G-F1 up to 70%. Interestingly, intracellular signaling events involved in cell proliferation, migration, and morphological change were up-regulated at 1 h incubation but down-regulated at 12 h. Therefore, our results suggest that G-F1 can be applied as a novel anti-skin cancer drug with anti-proliferative and anti-migration features.

• 한국환경성돌연변이발암원학회지
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• 제20권1호
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• pp.14-20
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• 2000

DHAQ-97, (2-(3-[p-bis(2-chloroethyl)aminophenyl]-2 formylaminopropanoyloxy) methy1-1,4-dihy-droxy-9,10-anthraquinone), is a novel anthraquinone derivative synthesized for use as an anti-neoplastic agent. In the present study, we have evaluated the selective cytotoxicity of DHAQ-97 by comparing its effects on viability and proliferation of human breast cancer cell line (NCF-7) versus normal immortalized breast epithelial cell line (MCF-10A). Thus, DHAQ-97 reduced both viability and proliferation of MCF-7 cells to a much greater extent than did for MCF-10A cells. The growth inhibitory and anti-proliferative properties of DHAQ-97 appear to be attributable to its ability to induce apoptosis as revealed by positive staining after in 냐셔 nick-end labeling (TUNEL), cleavage of poly(ADP-ribose)polymerase, release of mitochondrial cytochrome c into cytoplasm, and increased expression of pro-apoptotic Bax protein. Recent studies have indicated possible involvement of the ubiquitous eukaryotic transcription factor, NF-kappa B (NF-kB) in the regulation of apoptotic cell death. In line induced cytotoxicity in cultured MCF-7 cells. Furthermore, mild activation of NF-kB, as determined by its increased DNA binding capability, was observed 30 min after treatment with 10$\mu\textrm{m}$ DHAQ-97. Taken together, the above findings suggest that DHAQ-97 exerts selective cytotoxicity towards cancer cells through induction of apoptosis, which appears to be regulated by NF-kB.