• 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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.210-210
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• 2002

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 NEW STRATEGY FOR DRUG DEVELOPMENT IN POST-GENOMIC ERA(대한약학회)
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• pp.152.2-153
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• 2000

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2003년도 제40회 국제학술심포지움
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• pp.129-129
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• 2003

• 대한한방부인과학회지
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• 제28권1호
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• pp.46-57
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• 2015

Objectives: This study was designed to investigate the effects of Trogopterorum Faeces on the apoptostic cell death in breast cancer cells. Methods: In the experiment, the effects of Trogopterorum Faeces on proliferation rates and type of cell death were investigated using MCF-7 cells in vitro. The effects on expression levels of caspase 3 and caspase 9 were also investigated. Results: The effects on expression levels of caspase 3 and caspase 9 were also investigated. In the present results, treatment with Trogopterorum Faeces decreased proliferation rates in a dose dependent manner. $ID_{50}$ (50 % inhibitory dosage) was $177.2{\mu}g/ml$. In addition, treatment with Trogopterorum Faeces increased percentage of apoptotic cells. Finally the expression level of caspase 3 and caspase 9 were elevated by treatment with Trogopterorum Faeces respectively. Conclusions: This study suggests that Trogopterorum Faeces can trigger caspase dependent apoptosis in MCF-7 cells.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.473-481
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• 2020

Axl receptor tyrosine kinase has been implicated in cancer progression, invasion, and metastasis in various cancer types. Axl overexpression has been observed in many cancers, and selective inhibitors of Axl, including R428, may be promising therapeutic agents for several human cancers, such as breast, lung, and pancreatic cancers. Here, we examined the cell growth inhibition mediated by R428 and auranofin individually as well as in combination in the human breast cancer cell lines MCF-7 and MDA-MB-231 to identify new advanced combination treatments for human breast cancer. Our data showed that combination therapy with R428 and auranofin markedly inhibited cancer cell proliferation. Isobologram analyses of these cells indicated a clear synergism between R428 and auranofin with a combination index value of 0.73. The combination treatment promoted apoptosis as indicated by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. Cancer cell migration was also significantly inhibited by this combination treatment. Moreover, we found that combination therapy significantly increased the expression level of Bax, a mitochondrial proapoptotic factor, but decreased that of the X-linked inhibitor of apoptosis protein. Furthermore, the suppression of cell viability and induction of Bax expression by the combination treatment were recovered by treatment with N-acetylcysteine. In conclusion, our data demonstrated that combined treatment with R428 and auranofin synergistically induced apoptosis in human breast cancer cells and may thus serve as a novel and valuable approach for cancer therapy.

• 한국식품저장유통학회지
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• 제24권2호
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• pp.289-293
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• 2017

버려지는 마늘껍질의 자원으로써의 활용 가치를 확인하기 위해 마늘껍질 70% 에탄올 추출물(GPE)을 이용하여 인체에서 유래된 폐암 세포(A549), 위암 세포(AGS), 유방암 세포(MCF-7), 간암 세포(Hep3B) 및 대장암 세포(HT-29)의 생존율에 미치는 영향을 확인하였다. 폐암 세포(A549)의 경우 $200{\mu}g/mL$의 저 농도에서는 A549 세포의 생존율이 100%로 증식 억제 효과가 나타나지 않았으나 $500{\mu}g/mL$ 이상의 농도에서는 A549 세포의 생존율이 10% 이하로 떨어지면서 우수한 폐암 세포 증식 억제활성이 확인되었다. 위암 세포에 대한 조사에서는 $1,000{\mu}g/mL$의 농도에서 55%의 생존율을 확인할 수 있었고, 최고 $2,000{\mu}g/mL$의 농도에서 71%의 위암 세포 증식 억제활성이 확인되었다. 유방암 세포(MCF-7)의 경우 $200{\mu}g/mL$의 저 농도에서 78%, $500{\mu}g/mL$ 이상의 농도 처리 결과에서는 모두 90% 전후의 유방암 세포 증식 억제활성이 확인되었다. 간암 세포의 경우 $100{\mu}g/mL$의 저 농도에서도 57%의 억제 활성이 확인되어, GPE의 매우 우수한 간암 세포 증식 억제 활성이 확인되었고, 처리되는 GPE의 농도가 증가함에 따라 $500{\mu}g/mL$ 농도까지 농도 의존적으로 간암 세포에 대한 증식 억제 활성은 증가되어 간암 세포의 생존율이 13%까지 저하되었다. 대장암 세포(HT-29)의 경우 $200{\mu}g/mL$의 저 농도 처리에서 15%, $500{\mu}g/mL$ 농도 처리에서 85%, $1,000{\mu}g/mL$의 고농도 처리에서 93%의 간암세포 증식 억제율이 확인되었으며, 농도 의존적으로 간암 세포에 대한 생장 억제 효과가 있는 것으로 확인되었다. 이상의 결과를 종합해 볼 때 마늘껍질 70% 에탄올 추출물 GPE는 조사된 제일 낮은 농도($100{\mu}g/mL$)에서도 간암 세포의 증식을 57% 억제하는 우수한 활성이 확인되었고, $200{\mu}g/mL$의 저 농도 범위에서는 유방암과 간암 세포의 증식을 72-78% 억제하는 높은 활성이 확인되었으며, $500{\mu}g/mL$ 이상의 농도에서는 위암 세포를 제외한 조사된 4종류의 암세포(폐암, 유방암, 간암 및 대장암 세포)의 증식을 85-90% 억제하는 우수한 활성이 확인되었다. 본 연구의 결과를 통해 마늘 가공 과정에서 쓰레기로 버려지고 있는 마늘껍질은 70% 에탄올 추출을 통해 유방암(MCF-7), 폐암(A549), 위암(AGS), 유방암(MCF-7) 및 간암(Hep3B) 세포의 성장을 억제하는 활성 물질로서의 재활용 가치가 높은 것으로 확인되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6739-6742
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• 2013

Background: Breast cancer is a major health problem worldwide. Olive oil induces apoptosis in some cancer cells due to phenolic compounds like oleuropein. Although oleuropein has anticancer activity, the underlying mechanisms of action remain unknown. The study aimed to assess the mechanism of oleuropin-induced breast cancer cell apoptosis. Materials and Methods: p53, Bcl-2 and Bax gene expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in luminal MCF-7 cells. Results: Oleuropein-induced apoptosis was accompanied by up-regulation of both p53 and Bax gene expression levels and down-regulation in Bcl2. Conclusions: Oleuropein induces apoptosis in breast tumour cells via a p53-dependent pathway mediated by Bax and Bcl2 genes. Therefore, oleuropein may have therapeutic potential in breast cancer patients by inducing apoptosis via activation of the p53 pathway.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.90-90
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• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47D and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 추계국제학술대회
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• pp.180-180
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• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER Positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47B and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.