• 한국식품위생안전성학회지
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• 제22권3호
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• pp.209-212
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• 2007

내분비 교란 물질 중에서 최근에 문제가 되고 있는 물질이 프탈레이트계통 물질로서 플라스틱의 가소제로 사용하고 있는 DEHP와 DBP에 대하여 사람유방암세포 이면서 에스트로젠 의존성을 가지고 있는 MCF-7 세포에서의 세포 증식 정도를 농도 별로 측정하여 두 물질의 에스트로젠 작용가능성에 대하여 조사하였다. 시험물질인 DEHP와 DBP의 MCF-7 세포의 최대 증식 시의 농도를 조사해 본 결과, DEHP는 $17{\beta}-Estradiol$에 비하여 100배정도 높은 농도인 $10^{-7}M$ 에서 최대 증식능력을 보였고, DBP는 10배정도 높은 $10^{-8}M$ 에서 최대 증식능력을 보였다. 최대 증식 능력을 보일 때의 양성대조물질인 $17{\beta}-Estradiol$와 증식 정도 차이를 비교하였을 때에는 DEHP는 양성대조군 대비 87.5%의 증식 정도를 나타내었고, DBP는 73.4%의 증식 정도를 나타내었다 결론적으로 DEHP와 DBP 두 물질 모두 MCF-7 세포의 증식에 영향을 주는 것으로 판단되었으며, 최대 작용농도에 있어서는 DBP>DEHP, 세포 증식 정도에 있어서는 DEHP>DBP 인 것으로 판단되어 진다.

• Journal of Applied Biological Chemistry
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• 제58권3호
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• pp.219-226
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• 2015

본 연구에서는 레몬 잎 메탄올 추출물(MLL)의 인간 유방암 줄기 세포인 MCF-7-SC에 대한 항암 활성을 조사하였다. MLL이 MCF-7-SC에서 apoptosis를 유도하였으며, 이를 apoptotic body의 형성, sub-G1 phase 및 annexin V-positive 세포와 Bax/Bcl-2 ratio의 증가, caspase-9과 caspase-3의 활성화 및 PARP의 절 단을 통하여 확인하였다. 동시에 MCF-7-SC에서 MLL은 acidic vesicular organelles의 형성, LC3-II의 축적 증가, Akt/mTOR/p70S6K의 활성 억제 등을 통하여 autophagy를 유도하였다. Epithelial-mesenchymal transition (EMT)는 세포가 전이 상태를 획득하기 위한 중요한 과정이며, 이 기작은 암세포가 전이되는 것을 억제함에 있어서 중요한 표적이 된다. 낮은 농도에서의 MLL은 epithelial 마커 단백질인 E-cadherin이 증가와 mesenchymal 마커 단백질인 Snail과 Slug의 발현 감소를 통해 EMT 과정을 저해함으로써 MCF-7-SC에서 항전이 활성을 나타내었다. 본 연구에서는 레몬 잎 메탄올 추출물이 농도 의존적으로 유방암 줄기세포에 대해 세포 독성과 항전이 활성을 나타내고 있으며, 따라서 레몬잎은 항암 소재로서의 개발 가능성이 높은 식물이라고 사료된다.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 춘계학술대회
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• pp.117-117
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• 2004

• Journal of Pharmaceutical Investigation
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• 제41권6호
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• pp.381-386
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• 2011

Multi-drug resistance (MDR) has been known as a major hurdle in cancer chemotherapy. One of the most clinically significant causes of MDR was the efflux of anticancer agents mediated by p-glycoprotein (p-gp) over-expressed in MDR cancer cells. To overcome MDR, there have been several strategies such as co-administration with p-gp inhibitors and encapsulation of anticancer drugs into drug delivery systems. In the present study, curcumin was evaluated for its potential as p-gp inhibitor and MDR reversal activity when combined with paclitaxel incorporated into lipid nanoparticles (PTX/LN). Western blot assay showed curcumin did not modulate the level of p-gp expression in MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7, and over-expresses p-gp. However, curcumin inhibited p-gp-mediated efflux of calcein in a dose-dependent manner even though it showed lower activity compared to verapamil, a well-known p-gp inhibitor. Incorporation of paclitaxel into lipid nanoparticles partially recovered the anticancer activity of paclitaxel in MCF-7/ADR. The combined use of curcumin and PTX/LN exhibited further full reversal of MDR, suggesting susceptibility of PTX/LN to the efflux system. In conclusion, combined approach of using p-gp inhibitors and incorporation of the anticancer agents into nano-delivery systems would be an efficient strategy to overcome MDR.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.134-134
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• 2002

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.125-131
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• 2015

Currently, taxol is mainly extracted from the bark of yews; however, this method can not meet its increasing demand on the market because yews grow very slowly and are a rare and endangered species belonging to first-level conservation plants. Recently, increasing efforts have been made to develop alternative means of taxol production; microbe fermentation would be a very promising method to increase the production scale of taxol. To determine the activities of the taxol extracted from endophytic fungus N. sylviforme HDFS4-26 in inhibiting the growth and causing the apoptosis of cancer cells, on comparison with the taxol extracted from the bark of yew, we used cellular morphology, cell counting kit (CCK-8) assay, staining (HO33258/PI and Giemsa), DNA agarose gel electrophoresis and flow cytometry (FCM) analyses to determine the apoptosis status of breast cancer MCF-7 cells, cervical cancer HeLa cells and ovarian cancer HO8910 cells. Our results showed that the fungal taxol inhibited the growth of MCF-7, HeLa and HO8910 cells in a dose-and time-dependent manner. IC50 values of fungal taxol for HeLa, MCF-7 and HO8910 cells were $0.1-1.0{\mu}g/ml$, $0.001-0.01{\mu}g/ml$ and $0.01-0.1{\mu}g/ml$, respectively. The fungal taxol induced these tumor cells to undergo apoptosis with typical apoptotic characteristics, including morphological changes for chromatin condensation, chromatin crescent formation, nucleus fragmentation, apoptotic body formation and G2/M cell cycle arrest. The fungal taxol at the $0.01-1.0{\mu}g/ml$ had significant effects of inducing apoptosis between 24-48 h, which was the same as that of taxol extracted from yews. This study offers important information and a new resource for the production of an important anticancer drug by endofungus fermentation.

• Biomolecules & Therapeutics
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• 제26권3호
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• pp.322-327
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• 2018

A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.

• 한국식품영양과학회지
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• 제27권1호
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• pp.157-162
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• 1998

The antimutagenic activity of three kinds of extract such as fresh juice, ethanol extract and water extract of Artemisia iwayomogi against 3 - amino - 1, 4 - dimethyl - 5H - pyrido [4,3-b] indol (Trp-P-1) and N - methyl - N' - nitro - N -nitrosoguanidine(MNNG) was demonstrated with the Salmonella typhimurium assay. The number of revertants per plate decreased significantly when these extracts(0.5ug/plate) added to the assay system system using S. typhimurium TA 100. These extracts also showed prominant cytotoxic activity against four different kinds of human cancer cell as human lung cancer cell (A549), breast cancer cell(MCF7), fibrosacoma cell(HT1080) and gastric cancer cell(KATOIII), respectively.

• 대한핵의학회지
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• 제34권5호
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• pp.410-417
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• 2000

목적: 현재 유방암 치료제로서 임상실험 제 2단계에 들어간 idoxifene은 항에스트로겐 의약품으로서 기존의 tamoxifen보다도 많은 장점을 가지고 있는 것으로 연구결과 밝혀졌다. 또한 방사성 동위원소 $[^{123}I]$를 표지한 $[^{123}I]$idoxifene은 SPECT을 이용한 유방암세포를 영상화하여 조기에 진단할 수 있는 진단시약으로서 널리 각광 받고 있다. 따라서 본 연구에서는 idoxifene의 전구체를 합성하고 $[^{123}I]$를 표지하여 세포 내 섭취론 관찰하였다. 대상 및 방법: $[^{123}I]$idoxifene을 위한 전구체는 McCague가 연구 발표한 자료를 바탕으로 (2-chloroethoxy)benzene과 2-phenylbutanoic acid를 출발물질로 하여 합성하였다. 표지는 $[^{123}I]$를 사용하였으며 분리는 Silica Sep-Pak을 사용하였으며 세포 내 섭취실험은 에스트로겐 리셉터를 가진 MCF-7과 대조군으로서 에스트로겐 리셉터가 없는 MDA-MB-468을 이용하였다. 결과 및 결론: Idoxifene의 전구체인 4-stannylated 화합물의 합성수율은 약 30%이었으며, $[^{123}I]$ 표지는 60분 경과에서 $90{\sim}92%$로 최대의 표지수율을 보였으며 방사화학적 순도는 98%이상이었다. 또한 세포 내 섭취실험에서 실험군과 대조군 사이에 섭취비율은 180분에서 1.7:1로 나타나 idoxifence은 항에스트로겐 효과가 아주 높은 것으로 판명되었다. 이를 바탕으로 배양세포와 동물모델을 이용한 추가적인 실험이 필요하며, 유방암 환자에게도 임상이용이 기대된다.

• BMB Reports
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• 제52권12호
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• pp.706-711
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• 2019

Cisplatin (Cis-DDP) is one of the most widely used anti-cancer drugs. It is applicable to many types of cancer, including lung, bladder, and breast cancer. However, its use is now limited because of drug resistance. p90 ribosomal S6 kinase (p90RSK) is one of the downstream effectors in the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathway and high expression of p90RSK is observed in human breast cancer tissues. Therefore, we investigated the role of p90RSK in the Cis-DDP resistance-related signaling pathway and epithelial-mesenchymal transition (EMT) in breast cancer cells. First, we discovered that MDA-MB-231 cells exhibited more Cis-DDP resistance than other breast cancer cells, including MCF-7 and BT549 cells. Cis-DDP increased p90RSK activation, whereas the inactivation of p90RSK using a small interfering RNA (siRNA) or dominant-negative kinase mutant plasmid overexpression significantly reduced Cis-DDP-induced cell proliferation and migration via the inhibition of matrix metallopeptidase (MMP)2 and MMP9 in MDA-MB-231 cells. In addition, p90RSK activation was involved in EMT via the upregulation of mRNA expression, including that of Snail, Twist, ZEB1, N-cadherin, and vimentin. We also investigated NF-κB, the upstream regulator of EMT markers, and discovered that Cis-DDP treatment led to NF-κB translocation in the nucleus as well as its promoter activity. Our results suggest that targeting p90RSK would be a good strategy to increase Cis-DDP sensitivity in triple-negative breast cancers.