• 한국식품과학회지
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• 제32권4호
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• pp.964-969
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• 2000

랩 등 PVC 제품의 가소제인 DEHA의 에스트로겐 활성을 검색하기 위하여 내분비계 장애작용 중 에스트로겐성 작용을 검색하는 대표적인 방법인 in vitro E-screen assay와 OECD 및 미국 EPA EDSTAC에서 권고하고 있는 in vivo 난소절제 랫드를 이용한 자궁 비대반응시험(uterotrophic assay)을 실시하였다. 시험결과 $DEHA(5{\times}10^{-9}{\sim}5{\times}10^{-4}\;M)$는 MCF-7세포의 증식을 유발하지 않았고 난소절제 랫드에 200 mg/kg/day 용량까지 투여하여도 자궁 및 질 무게에 영향을 미치지 않았다. 따라서 본 실험결과 DEHA는 E-screen assay 및 자궁비대반응시험에서 에스트로겐성 작용이 없는 것으로 확인되었으나, 이들 물질의 에스트로겐성에 대한 결론을 내리기 위해서는 여러 종류의 in vitro 시험 data 및 in vivo 시험 data가 더 보충되어야 할 것으로 생각된다.

• Molecules and Cells
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• 제45권6호
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• pp.425-434
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• 2022

The post-translational modification (e.g., phosphorylation) of estrogen receptor α (ERα) plays a role in controlling the expression and subcellular localization of ERα as well as its sensitivity to hormone response. Here, we show that ERα is also modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability and transactivity of ERα, which in turn promotes breast cancer development. The elevation of ufmylation via the knockdown of UFSP2 (the UFM1-deconjugating enzyme in humans) dramatically increases ERα stability by inhibiting ubiquitination. In contrast, ERα stability is decreased by the prevention of ufmylation via the silencing of UBA5 (the UFM1-activating E1 enzyme). Lys171 and Lys180 of ERα were identified as the major UFM1 acceptor sites, and the replacement of both Lys residues by Arg (2KR mutation) markedly reduced ERα stability. Moreover, the 2KR mutation abrogated the 17β-estradiol-induced transactivity of ERα and the expression of its downstream target genes, including pS2, cyclin D1, and c-Myc; this indicates that ERα ufmylation is required for its transactivation function. In addition, the 2KR mutation prevented anchorage-independent colony formation by MCF7 cells. Most notably, the expression of UFM1 and its conjugating machinery (i.e., UBA5, UFC1, UFL1, and UFBP1) were dramatically upregulated in ERα-positive breast cancer cell lines and tissues. Collectively, these findings implicate a critical role attributed to ERα ufmylation in breast cancer development by ameliorating its stability and transactivity.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.563-567
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• 2012

In our era there has been several anti-cancer drugs which have undergone both experimental and clinical trials; however, due to their poor solubilities, numerous side effects, insufficient bioavailability and poor compliance, many have resulted into poor outcomes. Therefore, our aim was to investigate the effects of novel hydrophilic taxanes analogues CQMU-0517 and CQMU-0519 on growth of A549 lung, SKVO3 ovary and MCF7 breast carcinoma cell lines. Different concentrations of original paclitaxel, CQMU-0517, original docetaxel and CQMU-0519 were utilized on three cell lines, where cell growth was assessed using cell culture kit-8 and flow cytometry analysis. The results unveiled that CQMU-0517 and CQMU-0519 suppressed cell growth in the three particular cell lines, cell cycle arrest being evident in the G2/M phase. Hence, the results showed that these new taxane analogues have potential and warrant future clinical trials.

• 약학회지
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• 제41권6호
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• pp.718-723
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• 1997

In the course of developing novel antitumor intercalating agents, we synthesized 3- carbamoyloxymethyl-azaanthraquinones 6-12, incorporating the latent alkylating functionality. These compounds were designed to explore the effect of heteroatom incorporation into anthraquinone chromophore and the effect of the incorporation of the latent alkylating functionality. The derivatives were prepared by hetero Diels-Alder reaction as a key step followed by functionality of allylic methyl to the desired substituents. Growth inhibitory studies of the azaanthraquinones were conducted in vitro against human cancer cell lines (SNU-354: liver and MCF7: breast) and human epidermoid carcinoma cells that are sensitive (KB-3-1) and multidrug-resistant (KB-V-1). The derivatives were 10 to 100-fold less potent than doxorubicin against sensitive cell lines. However, they were marginally cross-resistant with doxorubicin against KB-V-1.

• Journal of Ginseng Research
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• 제36권2호
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• pp.169-175
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• 2012

Ginseng has been used as a traditional medicine for treatment of many diseases and for general health maintenance in people of all ages. Ginseng is also used to ameliorate menopausal systems. We investigated the estrogenic activity of Korean red ginseng (KRG) in a transient transfection system, using estrogen receptor (ER) and estrogen-responsive luciferase plasmids in MCF-7 cells. The extract activated both ER${\alpha}$ and ER${\beta}$. KRG modulated the mRNA levels of estrogen-responsive genes such as pS2 and ESR1 and decreased the protein level of ER${\alpha}$. In order to examine in vivo estrogenic activity of KRG, sixteen female Sprague-Dawley rats separated into four groups were studied for nine weeks: non-ovariectomized (OVX) rats treated with olive oil, OVX rats treated with olive oil, OVX rats treated with 17-${\beta}$-estradiol (E2) in olive oil, and OVX rats treated with KRG extract in olive oil. The experiments were repeated for three times and the data of twelve rats were combined. Body weight of OVX rats was greater than that of sham-operated control rats and was decreased by E2 treatment. Uterine weight increased after E2 treatment compared to OVX rats. However, no difference in body or uterine weight was observed with KRG intake. KRG induced reductions in total cholesterol, low density lipoprotein cholesterol/total cholesterol, high density lipoprotein cholesterol/total cholesterol, and low density lipoprotein cholesterol/high density lipoprotein cholesterol, but not to the same degree as did E2 intake. These results show that KRG does contain estrogenic activity as manifested by in vitro study but the activity is not strong enough to elicit physiological responses.

• Advances in nano research
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• 제7권4호
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• pp.241-248
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• 2019

Recent researches demonstrated well promising anticancer activities for antibiotics. Such effects would be significantly increased while nanoparticle based delivery systems were applied. In this study, the goal was aim to improve anticancer and antitoxic effects of Streptomycin by loading on special kind of dendrimer (anionic-linear-globular second generation). In the current study, Size and zeta potential as well as AFM techniques have been used to prove the fact that the loading was performed correctly. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the drug loaded on dendrimer nanoparticle were determined and compared with both of dendrimer alone and free drug with respect to staphylococcus aureus as the test microorganism. The anticancer activity among three groups including Streptomycin, Streptomycin -G2 dendrimer, and control was measured in vitro. In vitro studies showed that G2 anionic linear-globular polyethylene-glycol-based dendrimer, which loaded on Streptomycin was able to significantly improve the treatment efficacy over clinical Streptomycin alone with respect to proliferation assay. Maximal inhibitory concentration (IC50) was calculated to be $257{\mu}g/mL$ for streptomycin alone and $55{\mu}g/mL$ for Streptomycin -G2 dendrimer. In addition, Streptomycin -G2 dendrimer conjugate prevented the growth of MCF-7 cancerous cells in addition to enhance the number of apoptotic and necrotic cells as demonstrated by an annexin V-fluorescein isothiocyanate assay. Streptomycin -G2 dendrimer conjugate was able to increase Bcl-2/Bax ratio in a large scale compared with the control group and Streptomycin alone. Based on results a new drug formulation based nano-particulate was improved against S. aureus with sustained release and enhanced antibacterial activity as well as anticancer activity shown for functional cancer treatment with low side effects.

• 생명과학회지
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• 제27권8호
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• pp.919-929
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• 2017

본 연구는 발효 참당귀를 이용한 건강 기능성 식품개발을 위해 산청, 평창 및 제천산 참당귀를 Monascus purpureus로 발효시켜 제조한 발효 참당귀의 이화학적 특성 및 생리활성을 평가하였다. 발효 참당귀의 decursin 및 decursinol angelate 함량은 발효전보다 증가한 바, 평창 참당귀(PA)군의 615.504 및 326.742 ppm이 발효 후 각각 792.610 및 429.500 ppm으로 증가되었다. 총 페놀성 화합물과 플라보노이드 및 미네랄 함량이 발효로 인해 증가하였고, DPPH를 이용한 자유라디칼 소거능 및 Fe, Cu를 이용한 환원력 비교를 통해 발효 참당귀군에서 높게 나타났으며, 이중 FPA군에서 활성이 높은 것을 확인하였다. LPS처리 RAW 264.7세포의 NO생성능과 유방암 세포(MCF-7) 및 간암 세포(Hep3B) 성장 저해능 확인 결과 발효 참당귀군에서 활성이 높게 나타났다. 이와 같이 M. purpureus 발효 산청, 평창 및 제천 참당귀를 비교한 결과 평창 참당귀에서 건강 기능성 식품으로의 활용 가치가 높을 것으로 사료된다.

• BMB Reports
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• 제45권3호
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• pp.159-164
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• 2012

CD99 is known to be involved in the regulation of cell-cell adhesion. However, it remains unclear whether CD99 controls cell-extracellular matrix adhesion. In this study, the effects of CD99 activation on cell-extracellular matrix adhesion were investigated. It was found that engagement of CD99 with the stimulating antibody YG32 downregulated the adhesion of MCF-7 cells to fibronectin, laminin and collagen IV in a dose-dependent manner. The CD99 effect on cell-ECM adhesion was inhibited by overexpression of the dominant negative form of CD99 or CD99 siRNA transfection. Treatment of cells with $Mn^{2+}$ or by ${\beta}_1$ integrin-stimulating antibody restored the inhibitory effect of CD99 on cell-ECM adhesion. Cross-linking CD99 inactivated ${\beta}_1$ integrin through conformational change. CD99 activation caused dephosphorylation at Tyr-397 in FAK, which was restored by the ${\beta}_1$ stimulating antibody. Taken together, these results provide the first evidence that CD99 inhibits cell-extracellular matrix adhesion by suppressing ${\beta}_1$ integrin affinity.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6047-6053
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• 2012

Bracken fern [Pteridium aquilinem (L.) kuhn (Dennstaedtiaceae)] is one of the most common species on the planet. It has been consumed by humans and animals for centuries. Use by some human groups is because they believe bracken fern is good for health as plant medicine. However, it is also one of the few known plants that can cause tumors in farm animals. Many interested groups have focused their attention on bracken fern because of these interesting features. In order to evaluate the biological effects of exposure to this plant in cellular level, human cancer cell lines were treated with the fern dichloromethane extracts and the genotoxic and cytotoxic effects were studied. Anti-proliferative/cytotoxic effects were evaluated by cell count, MTT assay and flow cytometry methods with three different cancer cell lines, TCC, NTERA2, and MCF-7, and two normal cells, HDF1 and HFF3. Pro-apoptotic effects of the extracts were determined by DAPI staining and comet assay, on TCC cancer cells compared to the normal control cell lines. Cellular morphology was examined by light microscopy. Our present study showed that the extract caused DNA damage and apoptosis at high concentrations ($200{\mu}g/mL$) and also it may induce cell cycle arrest (G2/M phase) at mild concentrations (50 and $30{\mu}g/mL$) depending on the cell type and tumor origin. These results indicate that bracken fern extract is a potent source of anticancer compounds that could be utilized pharmaceutically.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9319-9325
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• 2014

Alkaloids are the most extensively featured compounds of natural anti-tumor herbs, which have attracted much attention in pharmaceutical research. In our previous studies, a mixture of major three alkaloid components (5, 6-dihydrobicolorine, 7-deoxy-trans-dihydronarciclasine, littoraline) from Hymenocallis littoralis were extracted, analyzed and designated as AHL. In this paper, AHL extracts were added to human liver hepatocellular cells HepG-2, human gastric cancer cell SGC-7901, human breast adenocarcinoma cell MCF-7 and human umbilical vein endothelial cell EVC-304, to screen one or more AHL-sensitive tumor cell. Among these cells, HepG-2 was the most sensitive to AHL treatment, a very low dose ($0.8{\mu}g/ml$) significantly inhibiting proliferation. The non-tumor cell EVC-304, however, was not apparently affected. Effect of AHL on HepG-2 cells was then explored. We found that the AHL could cause HepG-2 cycle arrest at G2/M checkpoint, induce apoptosis, and interrupt polymerization of microtubules. In addition, expression of two cell cycle-regulated proteins, CyclinB1 and CDK1, was up-regulated upon AHL treatment. Up-regulation of the Fas, Fas ligand, Caspase-8 and Caspase-3 was observed as well, which might imply roles for the Fas/FsaL signaling pathway in the AHL-induced apoptosis of HepG-2 cells.