• 생명과학회지
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• 제23권8호
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• pp.970-977
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• 2013

Epithelial-to-mesenchymal transition (EMT)는 embryogenesis에서 중요한 역할을 하며 tumor metastasis, invasion에도 관여함으로써 tumor progression 및 aggressiveness에 기여한다. EMT는 EMT hallmark인 epithelial E-cadherin의 발현 감소와 mesenchymal-like cell morphology를 획득함으로써 epithelial cell polarity를 잃어버리는 특징을 가지고 있다. $O_2{^-}$, $H_2O_2$, $OH^-$와 같은 활성산소가 EMT를 유도하는 것으로 알려져 있다. Snail이 E-cadherin의 발현을 억제함으로써 ROS에 의한 EMT에 관여하는 것으로 알려져 있으나, 그 기작은 완전히 밝혀져 있지 않다. 본 연구에서는, noninvasive breast tumor cell line인 MCF-7 세포에 Egr-1을 과발현시킨 후 그 영향을 조사하였다. Egr-1이 과발현되면, MCF-7 세포는 epithelial cell polarity를 잃고 spindle-shaped로 변화되므로, Egr-1이 EMT를 유도할 가능성이 대두되었다. 또한 Snail이 Egr-1에 의한 EMT에 관여함을 확인하였다. 나아가, 본 연구진은 Egr-1-Snail axis가 ROS에 의해 활성화 되고, ROS에 의한 EMT에서 중요한 역할을 함을 발견하였다.

• Nuclear Medicine and Molecular Imaging
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• 제41권5호
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• pp.364-372
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• 2007

목적 : 여러 종양영상용 방사성의약품이 암환자에서 치료후 반응을 보는 데 사용되고 있다. 이 연구에서는 paclitaxel 노출 시간에 따른 여러 종양영상용 방사성의약품의 유방암세포 섭취양상을 paclitaxel 노출 48시간까지 생존종양세포 수와 비교하여 알아보았다. 대상 및 방법 : F-18-fluorodeoxyglucose, C-11-methionine, Tl-201, Tc-99m-MIBI, Tc-99m-tetrofosmin의 5가지 종양영상용 방사성의약품의 MCF-7 유방암세포에서의 세포섭취를 알아보았다. DMSO 노출 대조군, 다양한 paclitaxel 노출시간을 가지는 5가지의 실험군(노출시간 2시간, 6시간, 12시간, 24시간, 48시간)의 총 6가지 조건에서 종양영상용 방사성의약품을 60분간 섭취시킨 뒤 섭취율을 구하였다. Paclitaxel은 10 nM과 100 nM의 2가지 농도를 사용하였다. 결과 : 10 nM의 paclitaxel은 노출 48시간까지 MCF-7 세포의 살아 있는 세포의 비율을 약 75% 정도로 감소시켰지만, 종양세포의 5가지 종양영상용 방사성의약품 섭취는 대조군과 비교시 유의하게 감소하지 않았다. 100 nM의 paclitaxel은 노출 48시간까지 MCF-7 세포의 살아 있는 세포의 비율을 약 55% 정도로 감소시켰지만, 종양세포의 5가지 종양영상용 방사성의약품 섭취는 대조군과 비교시 유의하게 증가하였다. 결론 : MCF-7 유방암세포주에서 종양영상용 방사성의약품인 F-18-FDG, C-11-methionine, Tl-201, Tc-99m-MIBI, Tc-99m-tetrofosmin의 섭취율은 paclitaxel 투여 후 48시간까지 생존 종양세포 수의 감소를 반영하지 못한다.

• Journal of Nutrition and Health
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• 제49권2호
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• pp.72-79
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• 2016

Purpose: The initiation of mandatory folic acid fortification using pteroylmonoglutamic acid (PteGlu) has reduced the rate of congenital malformations. However, it also appears to be responsible for several adverse effects, including increased cancer incidence. This may be related to physicho-chemical characteristics of PteGlu. This study examines the potential effect of high concentrations of PteGlu on a population subjected to mandatory folic acid fortification using an in vitro model. Methods: Caco-2 (colorectal cancer) and MCF7 (breast cancer) cell lines were cultured at 6 different PteGlu concentrations (0, 0.1, 1, 50, 250, and $500{\mu}g/ml$) for 6 days. Cell growth was determined using thiazolyl blue tetrazolium bromide assay. The genotype of dihydrofolate reductase 19bp deletion/insertion (DHFR 19-del) was also scored in cell lines using a restriction fragment length polymorphism technique to examine whether genetic variations may factor in cell proliferation. Results: PteGlu exhibited differential growth promoting properties between cell lines. Caco-2 cells did not show a significant growth difference at low concentrations compared to control, however, at higher concentrations, the growth showed a contrasting trend in the early experimental period, while MCF7 showed enhanced cell growth at all concentrations. The DHFR 19-del genotype differed in the two cell lines. Conclusions: Altered response to PteGlu by Caco-2 and MCF7 may reflect a tissue specific disease aetiology or genotype specific differential enzyme activity, for example by DHFR, to critical levels of PteGlu. As folic acid fortification is a blanket intervention, and DHFR and other enzyme activities vary between individuals, PteGlu intake may have an as yet undefined effect on health. These findings may be relevant when considering mandatory folic acid fortification for disease prevention.

• Molecular & Cellular Toxicology
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• 제1권3호
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• pp.149-156
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• 2005

Di (n-ethylhexyl) phthalate (DEHP) is thought to mimic estrogens in their action, and are called endocrine disrupting chemicals. DEHP is used in numerous consumer products, especially those made of flexible polyvinyl chloride and have been reported to be weakly estrogenic. In this study, DEHP were tested for estrogenic properties in vitro models and with microarray analysis. First, the E-screen assay was used to measure the proliferation of DEHP in MCF-7 cells, a human breast cancer cell line. DEHP induced an increase in MCF-7 cell proliferation at concentration of $10^{-4}M$. Second, we carried out a microarray analysis of MCF-7 cells treated with DEHP using human c-DNA microarray including 401 endocrine system related genes. Of the genes analyzed, 60 genes were identified showing significant changes in gene expression resulting from DEHP. Especially, 4 genes were repressed and 4 genes were induced by DEHP compared to $17{\beta}-estradiol$. Among these genes, trefoil factor 3 (intestinal), breast cancer 1, early onset and CYP1B1 are involved in estrogen metabolism and regulation. Therefore it suggests that these genes may be associated with estrogenic effect of the DEHP on transcriptional level. The rationale is that, as gene expression is a sensitive endpoint, alterations of these genes may act as useful biomarkers to define more precisely the nature and level of exposure to kinds of phthalates.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3191-3196
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• 2013

Leaf extracts of Cassia alata L (akapulko), traditionally used for treatment of a variety of diseases, were evaluated for their potential antitumor properties in vitro. MTT assays were used to examine the cytotoxic effects of crude extracts on five human cancer cell lines, namely MCF-7, derived from a breast carcinoma, SK-BR-3, another breast carcinoma, T24 a bladder carcinoma, Col 2, a colorectal carcinoma, and A549, a nonsmall cell lung adenocarcinoma. Hexane extracts showed remarkable cytotoxicity against MCF-7, T24, and Col 2 in a dose-dependent manner. This observation was confirmed by morphological investigation using light microscopy. Further bioassay-directed fractionation of the cytotoxic extract led to the isolation of a TLC-pure isolate labeled as f6l. Isolate f6l was further evaluated using MTT assay and morphological and biochemical investigations, which likewise showed selectivity to MCF-7, T24, and Col 2 cells with $IC_{50}$ values of 16, 17, and 17 ${\mu}g/ml$, respectively. Isolate f6l, however, showed no cytotoxicity towards the non-cancer Chinese hamster ovarian cell line (CHO-AA8). Cytochemical investigation using DAPI staining and biochemical investigation using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-a method used to detect DNA fragmentation-together with caspase assay, demonstrated apoptotic cell death. Spectral characterization of isolate f6l revealed that it contained polyunsaturated fatty acid esters. Considering the cytotoxicity profile and its mode of action, f6l might represent a new promising compound with potential for development as an anticancer drug with low or no toxicity to non-cancer cells used in this study.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.293.1-293.1
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• 2002

Pyrethroids are extensively used as insecticide in agriculture and home. Several studies have reported that yrethroids are relatively safe to humans and wildlife. However. some studies have suggested that pyrethroids ossess estrogen-like activity. Thus. the purpose of this study was to investigate the effects of pyrethroid ompounds on cell proliferation. and expression of ERs and pS2 using estrogen receptor positive human breast ancer cell line (MCF-7 BUS celis). (omitted)

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1757-1762
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• 2014

Development of drugs from natural products has been undergoing a gradual evoluation. Many plant derived compounds have excellent therapeutic potential against various human ailments. They are important sources especially for anticancer agents. A number of promising new agents are in clinical development based on their selective molecular targets in the field of oncology. D-pinitol is a naturally occurring compound derived from soy which has significant pharmacological activitites. Therefore we selected D-pinitol in order to evaluate apoptotic potential in the MCF-7 cell line. Human breast cancer cells were treated with different concentrations of D-pinitol and cytotoxicity was measured by MTT and LDH assays. The mechanism of apoptosis was studied with reference to expression of p53, Bcl-2, Bax and NF-kB proteins. The results revealed that D-pinitol significantly inhibited the proliferation of MCF-7 cells in a concentration-dependent manner, while upregulating the expression of p53, Bax and down regulating Bcl-2 and NF-kB. Thus the results obtained in this study clearly vindicated that D-pinitol induces apotosis in MCF-7 cells through regulation of proteins of pro- and anti-apoptotic cascades.

• Natural Product Sciences
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• 제18권4호
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• pp.244-249
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• 2012

Angelica acutiloba is one of the most intensively cultivated medicinal plants in Korea. The roots of this plant have been used as an important herbal drug, especially for the treatment of various female disorders, as the traditional therapy in Korea and other Asian countries. Consumption of its fresh leaves as a healthy vegetable has recently increased. In this study, essential oil fractions were extracted from the roots and leaves of this plant by steam distillation. Compositions of the two oils were compared by gas chromatography-mass spectrometry (GC-MS). The antibacterial activities of the essential oil were determined against three strains of Escherichia coli. DPPH radical scavenging and reducing power tests were performed to evaluateits antioxidant activities. The cytotoxic activities of the essential oil against a human breast and a uterine cancer cell line were estimated by MTT tests. Additionally, the morphological changes after treatment of the oil fraction were observed under a microscope. The essential oil fraction and its main components, Z-ligustilide and butylidene phthalide, inhibited the growth of three E. coli strains examined, with minimum inhibiting concentrations (MICs) ranging from 1.0 mg/ml to 8.0 mg/ml. Additionally, the essential oil fraction of A. acutiloba exhibited significant DPPH free radical scavenging activity and reducing power. Significant cytotoxic activities of the A. acutiloba essential oil were observed for human uterine (Hela) and breast (MCF-7) cancer cell lines.

• Archives of Pharmacal Research
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• 제25권4호
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• pp.550-555
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• 2002

The discovery and development of the taxane class of antitumor compounds represent significant advances in the treatment of patients with a variety of malignancies. These drugs are effectively used in the treatment of breast cancer. In this study we evaluated the efficacy of fractionated usage of both paclitaxel and docetaxel as a single agent in the breast cancer cell line MCF-7. It has been shown that the cytotoxic effect of paclitaxel was increased when the divided $IC_{50}$ concentrations were used sequentially and in contrast to paclitaxel, cytotoxic effect of docetaxel was decreased with the same schema and the single dose of $IC_{50}$ concentration was optimal. The cause of the difference between the cytotoxic effects of two agents with this schedule is obscure. Demonstrating mechanisms, which are responsible for these differences, will be important for more rational use of taxoids and to provide basis for the following clinical trials.

• 한국환경성돌연변이발암원학회지
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• 제22권4호
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• pp.274-278
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• 2002

Phthalates, suspected endocrine disruptor, are plasticizer and solvent used in industry, and some phthalates are known as potential carcinogen. Most common human exposure to this compounds may occur with contaminated food. It may migrate into food from plastic wrap or may enter food from general environmental contamination, and it has become widespread environmental pollutants, thus leading to a variety of phthalates that possibly threaten the public health. Dibutyl phthalate (DBP) may playa part of cell proliferator, which mediates changes in gene expression and the metabolism of xenobiotics. An understanding of the role of DBP in modulating gene regulation should provide insight regarding mechanisms of DBP induced xenoestrogenic impact. To elucidate the type of genes that are associated with estrogenic activity induced by DBP at the dose (10$^{-8}$ M) appeared proliferating effects, the pattern of gene expression in MCF7 cells was compared between 17$\beta$-estradiol and DBP exposure in the cDNA microarray. From the results, it showed some differences of gene expression patterns between MCF7 cells treated with 17$\beta$-estradiol and DBP, and also DBP shows estrogenic potential with changes in estrogen-related gene expression levels.