• Journal of Nutrition and Health
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• v.46 no.6
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• pp.503-510
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• 2013

Breast cancer is the most common malignancy in women, both in the developed and developing countries. Anthocyanins are natural coloring of a multitude of foods, such as berries, grapes or cherries. Glycosides of the aglycons delphinidin represent the most abundant anthocyanins in fruits. Delphinidin has recently been reported to inhibit the growth of human tumor cell line. Also, delphinidin is a powerful antioxidant that reportedly exerts beneficial effects in patients with advanced cancer by reducing the level of reactive oxygen species and increasing glutathion peroxidase activity. This study investigates the effects of delphinidin on protein ErbB2, ErbB3 and Akt expressions associated with cell proliferation and Bcl-2, Bax protein associated with cell apoptosis in MDA-MB-231 human breast cancer cell line. MDA-MB-231 cells were cultured with various concentrations (0, 5, 10, and $20{\mu}mol/L$) of delphinidin. Delphinidin inhibited breast cancer cell growth in a dose dependent manner (p < 0.05). ErbB2 and ErbB3 expressions were markdly lower $5{\mu}mol/L$ delphinidin (p < 0.05). In addition, total Akt and phosphorylated Akt levels were decreased dose-dependently in cells treated with delphinidin (p < 0.05). Futher, Bcl-2 levels were dose-dependently decreased and Bax expression was significantly increased in cells treated with delphinidin (p < 0.05). In conclusion, I have shown that delphinidin inhibits cell growth, proliferation and induces apoptosis in MDA-MB-231 human breast cancer cell lines.

• The Journal of Korean Obstetrics and Gynecology
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• v.28 no.2
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• pp.15-25
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• 2015

Objectives : In this study, we investigated the anti-proliferative and apoptosis inducing effect of water extract of Chelidonium majus (CM) on human breast cancer cell MDA-MB-231. Methods : The MTT assay was used to assess cell proliferation. The expression of apoptosis related gene was assessed by quantitative Real-time PCR. Cell apoptosis detected by flow cytometry using Annexin-V/PI staining. Results : Our data revealed that CM inhibited the cell growth in a dose dependent manner (0, 62.5, 125, 250, 500 μg/ml). CM increased mRNA expression of pro-apoptotic genes Bax, caspase-3, and caspase-9. Annexin-V/PI staining assays revealed that apoptosis-induced cell death increased in a dose-dependent manner in cells. Conclusions : CM induces cell death in MDA-MB-231 human breast cancer cell and shows potentials for use in cancer therapy as apoptosis-inducing agent.

• Microbiology and Biotechnology Letters
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• v.47 no.1
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• pp.34-42
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• 2019

Apigenin, a common natural product that is found in many plants and vegetables, has been reported to have many biological activities, including antioxidative, anti-inflammatory, and anticancer effects. The triple-negative breast carcinoma cell line MDA-MB-231 is known to be highly invasive and resistant to chemotherapy. In this study, we investigated the anticancer effect of apigenin on human MDA-MB-231 cells. First, the cytotoxicity of apigenin toward MDA-MB-231 cells was analyzed by MTT assay. Then, the cell cycle and apoptotic effects of apigenin were examined, and the molecular mechanism underlying its anticancer activity was explored. Apigenin inhibited the growth of the cells in a dose-dependent manner, correlating with the cell cycle arrest at the G2-M phase as well as an increase of early apoptosis. The cell-cycle inhibitory effect was highly associated with the increased expression of p21 and decreased expression of CDK6, cyclin D1, and cyclin B1. The induction of apoptosis by apigenin was associated with the upregulated expression of cleaved PARP and cleaved caspase-3, -7, and -9.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.12
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• pp.1654-1661
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• 2011

We investigated the effect of Angelica keiskei ethanol (AKE) extract on cell death in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the presence 125, 150 and 175 ${\mu}g$/mL concentrations of AKE for 24 hours. MTT assays demonstrated that mitochondrial dehydrogenase activities decreased in a dose-dependent manner in MDA-MB-231 cells (p<0.05). In contrast, the proportion of dual staining with Hoechst 33342/ethidium bromide(EtBr) for cell death increased in a dose-dependent manner in MDA-MB-231 cells (p<0.05). In particular, the levels of cell death caused by apoptotic program showed marked increases in the 150 and 175 ${\mu}g$/mL AKE groups, as revealed by flow cytometry. An apoptotic suppressor gene, Bcl-2, significantly decreased at the transcript level (p<0.05). The expression levels of proapoptotic genes, both Bax and caspase 3 significantly increased (p<0.05). Furthermore, the ratio of Bcl-2/Bax mRNA which is considered to be an important indicator of apoptosis, significantly decreased in a dose-dependent manner (p<0.05). These results taken together indicate that, the AKE extract used in this study induces cell death in MDA-MB-231 human breast cancer cells.

• The Journal of Korean Obstetrics and Gynecology
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• v.28 no.2
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• pp.26-39
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• 2015

Objectives : Dendropanax morbifera is known as a tree that has been used in traditional medicine for various diseases. However, its biological activities in cancer have not yet been clearly elucidated. In this study, we investigated the anti-cancer effects of water extract of Dendropanax morbifera (DP) on 2 human breast cancer cell lines (estrogen dependent MCF-7 and estrogen independent MDA-MB-231). Methods : The MTT assay and flow cytometry were used to assess cell proliferation, along with cell cycle analysis. Nitric oxide production was detected by Griess assay. The expression of apoptosis related gene was assessed by quantitative real-time PCR. Results : Our data revealed that DP inhibits the cell growth in a dose dependent manner (0, 50, 100, 250, and 500 μg/ml) of both estrogen independent MDA-MB-231 and estrogen dependent MCF-7 breast cancer cells. Also, LPS induced nitric oxide production was significantly reduced by DP. Cell cycle analysis showed an increased G1 phase in the MCF-7 cell and G2/M phase in the MDA-MB-231 cell. DP decreased mRNA expression of apoptotic suppressor gene Bcl-xL, and increased mRNA expression of pro-apoptotic genes. DP increased mRNA expression of p21, and Rip1 in both cell. And DP decreased mRNA expression of survivin in the MCF-7 cell. Conclusions : Taken together, these results indicate that DP extract are source of anti-cancer potential and could be developed botanical drug.

• Preventive Nutrition and Food Science
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• v.12 no.1
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• pp.11-15
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• 2007

This study was conducted to evaluate the influence of diets containing genistein and soy extract on the growth of MDA-MB-231 cells implanted into female Balb/c mice. Four-week-old female athymic nude mice (Balb/c) were acclimated to an AIN-93G control diet for 1 week and then injected MDA-MB-231 cells ($1{\times}10^6$/site) and were continued on the on AIN-93G control diet. Five weeks after injecting the MDA-MB-231 cells ($1{\times}10^6$/site), two experimental groups were assigned to diets containing genistein (750 ${\mu}g/g$ AIN-93G diet) or 0.6% soy extract (containing genistein at 750 ${\mu}g/g$ AIN-93G diet) until they were sacrificed. Tumor growth was significantly reduced in the groups treated with genistein and soy extract compared to the control group. The results of the proliferating cell nuclear antigen (PCNA) assay also revealed that genistein and soy extract treatment reduced the proliferation of MDA-MB-231 cells in vivo. In the present study, dietary isoflavone was provided just before solid tumor formation, and thus the timing of dietary isoflavone administration may be critical to the suppression of tumor growth.

• Biomolecules & Therapeutics
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• v.22 no.6
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• pp.540-546
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• 2014

The high mortality rates associated with cancer reflect the metastatic spread of tumor cells from the site of their origin. Metastasis, in fact, is the cause of 90% of cancer deaths. Therefore, considerable effort is being made to inhibit metastasis. In the present study, we screened ketotifen for anti-migratory and anti-invasive activities against MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer cells. Cancer cell migration and invasion were measured using multi-well chambers. Additionally, western blots were used to examine the effects of ketotifen on the expressions of CDC42, Rho, Rac, and matrix metalloproteinase 9 (MMP-9). The results showed that ketotifen dose-dependently suppressed the migration and invasion of MDA-MB-231 and HT-1080 cells. Ketotifen also suppressed the expressions of CDC42, Rac, and Rho, which, significantly, are involved in MDA-MB-231 and HT-1080 cancer cell migration. Moreover, ketotifen suppressed the expression and activity of MMP-9, which is involved in degradation of the extracellular matrix leading to invasion. The overall data suggested that ketotifen suppresses the migration and invasion of MDA-MB-231 and HT-1080 cancer cells via inhibition of CDC42, Rac, Rho, and MMP-9 expression.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.494-502
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• 2018

Breast cancer is currently the most prevalent cancer in women, and its incidence increases every year. Azole antifungal drugs were recently found to have antitumor efficacy in several cancer types. They contain an imidazole (clotrimazole and ketoconazole) or a triazole (fluconazole and itraconazole) ring. Using human breast adenocarcinoma cells (MCF-7 and MDA-MB-231), we evaluated the effects of azole drugs on cell proliferation, apoptosis, cell cycle, migration, and invasion, and investigated the underlying mechanisms. Clotrimazole and ketoconazole inhibited the proliferation of both cell lines while fluconazole and itraconazole did not. In addition, clotrimazole and ketoconazole inhibited the motility of MDA-MB-231 cells and induced $G_1$-phase arrest in MCF-7 and MDA-MB-231 cells, as determined by cell cycle analysis and immunoblot data. Moreover, Transwell invasion and gelatin zymography assays revealed that clotrimazole and ketoconazole suppressed invasiveness through the inhibition of matrix metalloproteinase 9 in MDA-MB-231 cells, although no significant changes in invasiveness were observed in MCF-7 cells. There were no significant changes in any of the observed parameters with fluconazole or itraconazole treatment in either breast cancer cell line. Taken together, imidazole antifungal drugs showed strong antitumor activity in breast cancer cells through induction of apoptosis and $G_1$ arrest in both MCF-7 and MDA-MB-231 cells and suppression of invasiveness via matrix metalloproteinase 9 inhibition in MDA-MB-231 cells. Imidazole drugs have well-established pharmacokinetic profiles and known toxicity, which can make these generic drugs strong candidates for repositioning as antitumor therapies.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.9
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• pp.1114-1119
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• 2008

Among the numerous polyphenols isolated from green tea, epigallocatechin gallate (EGCG) is a predominate and is considered to be a major therapeutic agent. To elucidate the mechanical insights of anti-tumor effect, EGCG was applied to human breast cancer MDA-MB-231 cells. We investigated the effect of EGCG on protein and mRNA expression of proteins related to cell apoptosis in MDA-MB-231 human breast cancer cell lines. We also identified caspase-3 activity. We cultured MDA-MB-231 cells in the presence of 0, 5, 10, and $20\;{\mu}M$ of EGCG. Protein and mRNA expression of bcl-2 were decreased dose-dependently in cells treated with EGCG. However, protein and mRNA expression of bax were increased (p<0.05). Caspase-3 activities were increased dose-dependently in cells treated with EGCG. These results suggest that EGCG induces cell apoptosis by increase of caspase activity through decreasing of protein and mRNA expression of bcl-2 and increasing of protein and mRNA expression of bax.

• Journal of Nutrition and Health
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• v.38 no.2
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• pp.104-111
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• 2005

Tumor invasion is composed of four steps: cell adhesion to the extracellular matrix, degradation of the extracellular matrix components, tumor cell motility followed by cell detachment. Matrix metalloproteinases (MMPs) are important proteinases that associated with degradation of matrix component. Epigallocatechin gallate (EGCG) is a major polyphenotic constituent of green tea. In the study, we examined the anti-invasive and MMP activity suppression effects of EGCG in MDA-MB-231 human breast cancer cells. MDA-MB-23l human breast cancer cells were cultured with various concentrations 0 - 100 μM of EGCG. EGCG significantly inhibited the cell adhesion to the fibronectin. Cell motility through gelatin filter and invasion to Matrigel were inhibited dose-dependently by EGCG treatment. EGCG also inhibited the activities of MMP-2, -9 and the amount of MMP-9 (α = 0.05). Therefore, EGCG may contribute to the potential beneficial food component to prevent the invasion and metastasis in breast cancer. (Korean J Nutrition 38(2): 104～111, 2005)