• Journal of Life Science
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• v.15 no.5 s.72
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• pp.802-808
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• 2005

Human Disabled-2 (Dab2) is a candidate tumor suppressor gone that regulates cell growth by c-Fos suppression in normal cells. In many cancer cells, Dab2 expression is lost or greatly diminished in $\∼85\%$ of the breast and ovarian cancers. In this study, we have examined the methylation status of CpG island on Dab2 gene promoter using bisulfite-assisted genomic sequencing and methylation specific PCR (MSP) method in human breast cancer cell line, MDA MB-231 cells. In normal human uterus endometrial cells, Dab2 was completely unmethylated. In contrast, Dab2 was methylated on CpG dinucleotides near the TATA_ box in MDA MB-231 cells. following MDA MB-231 cells by treatment with 5-azacytidine, Dab2 gene were demethylated and reexpressed. Result of this study suggested that silencing of Dab2 gene is correlated to CpG island methylation in human breast cancer cell line, MBA MD-231 cells.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10819-10824
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• 2015

Aims: To explore the effect and probable mechanism of a synthetic retinoid 4-amino-2-tri-fluoromethylphenyl ester (ATPR) on apoptosis of MDA-MB-231 breast cancer cells. Materials and Methods: MTT assays were performed to measure the proliferation of MDA-MB-231 cells treated with different concentrations of all-trans retinoic acid (ATRA) and ATPR. Morphologic changes were observed by microscopy. The apoptosis rates and cell cycling of MDA-MB-231 cells treated with ATRA or ATPR were assessed using flow cytometry analysis. Expression of retinoic acid receptor and phosphorylation of ERK, JNK, p38 proteins were detected by Western blotting. Results: Treatment of the cells with the addition of $15{\mu}mol/L$ ATPR for 48 h clearly demonstrated reduced cell numbers and deformed cells, whereas no changes in the number and morphology were observed after treatment with ATRA. The apoptosis rate was 33.2% after breast cancer MDA-MB-231 cells were treated by ATPR ($15{\mu}mol/L$) whereas ATRA ($15{\mu}mol/L$) had no apoptotic effect. ATPR inhibited the phosphorylation of ERK, JNK, and p38 while ATRA had no significant effect. ATPR inhibited the expression of BiP and increased the expression of Chop at the protein level compared with control groups, ATRA and ATPR both decreased the protein expression of $RXR{\alpha}$, ATPR reduced the protein expression of $RAR{\beta}$ and $RXR{\beta}$ while ATRA did not decrease $RAR{\beta}$ or $RXR{\beta}$. Conclusions: ATPR could induce apoptosis of breast cancer MDA-MB-231 cells, possible mechanisms being binding to $RAR{\beta}/RXR{\beta}$ heterodimers, then activation of ER stress involving the MAPK pathway.

• KSBB Journal
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• v.31 no.1
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• pp.52-57
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• 2016

Mutant p53 (R280K) is highly expressed in MDA-MB-231 triple-negative human breast cancer cells. Currently, we reported the role of mutant p53-R280K in mediating the survival of MDA-MB-231 cells in vitro. The present study was undertaken to determine whether mutant p53-R280K affects breast cancer cell growth in vivo. To this end, we used small interfering RNA to knockdown the level of mutant p53-R280K in MDA-MB-231 cells. Silencing of mutant p53-R280K in MDA-MB-231 cells causes substantial tumor regression of established xenografts in vivo. In xenograft model for breast cancer, silencing of mutant p53-R280K in MDA-MB-231 cells significantly inhibited the tumor growth. Moreover, TUNEL assay showed more occurrence of apoptotic cells in mutant p53-R280K silenced tumors compared to control. Our data indicate that mutant p53-R280K has an important role in mediating tumor growth of MDA-MB-231 cells in vivo. Taken together, this study suggests that endogenous mutant p53-R280K could be used as a therapeutic target for breast cancer cells harboring this TP53 missense mutation.

• Journal of Microbiology and Biotechnology
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• v.27 no.1
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• pp.36-42
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• 2017

In this work, we isolated a surface layer protein (SLP) from a Bacillus thuringiensis (Bt) strain to evaluate it cytotoxic effects against MDA-MB-231 human breast cancer cells. AP11 was selected from a g roup of Bt strains using SLP olig onucleotides developed from Bacillus conserved regions. The AP11 strain was grown in Luria Bertani medium until the late exponential phase; an 86 kDa protein was extracted using 5 M LiCl and identified by liquid chromatography-tandem mass spectrometry. It corresponded to a multispecies SLP highly similar to previously described SLPs in Bt. The MDA-MB-231 breast cancer cells $LC_{50}$ was obtained using $0.25{\mu}g/ml$ of the isolated SLP. HaCat non-cancerous cells presented 90% survival using the same protein concentration. Our data suggest that SLP cytotoxicity against MDA-MB-231 could be induced by an interaction with the CDH11 cell membrane receptor.

• 대한동의생리학회:학술대회논문집
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• 2005.07a
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• pp.21-21
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• 2005

• The Journal of Internal Korean Medicine
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• v.35 no.2
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• pp.133-144
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• 2014

O. diffusa, C. appendiculata and F. thunbergii are reported to possess many pharmacological activities including anti-oxidant, anti-inflammatory, anti-hypertension, anti-diabetic and anti-cancer effects. However, their anti-cancer activities in human breast cancer have not been clearly elucidated yet. Objectives: In the present study, we compared the in vitro cytotoxic effects of single and complex treatment of O. diffusa, C. appendiculata and F. thunbergii in human breast cancer MDA-MB-231 cells. Methods: After we treated human breast cancer MDA-MB-231 cells with O. diffusa, C. appendiculata and F. thunbergii. we evaluated viability, growth inhibition, morphological changes, apoptotic body formation, measurement of the cell cycle and formation of DNA fragmentation of these cells. Results: We found that single treatment of O. diffusa and F. thunbergii could inhibit cell proliferation in human breast cancer MDA-MB-231 cells. However, complex treatment of O. diffusa, C. appendiculata and F. thunbergii had weak or no effect on the cell proliferation of MDA-MB-231 cells. The first, anti-proliferative effects of O. diffusa in MDA-MB-231 cells was associated with G2/M arrest of cell cycle and apoptotic cell death. The second, anti-proliferative effect of F. thunbergii in MDA-MB-231 cells was associated with apoptotic cell death. Conclusions: Taken together, these findings suggest that O. diffusa and F. thunbergii may be a potential chemotherapeutic agent for the control of human breast cancer cells, further studies will be needed to identify the molecular mechanisms.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.8
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• pp.983-988
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• 2007

Epigallocatechin gallate (EGCG), a principal antioxidant derived from green tea, is one of the most extensively investigated chemopreventive phytochemicals. However, the effect of EGCG on proliferation in MDA-MB-231 breast cancer cell is not well known. We investigated the effect of EGCG on protein and mRNA expression related to cell proliferation in MDA-MB-231 human breast cancer cell lines. We cultured MDA-MB-231 cells in the presence of 0, 5, 10 and 20 ${\mu}m$ of EGCG. EGCG significantly inhibited the cancer cell proliferation (p<0.05). In MDA-MB-231 huamn breast cancer cell, EGCG lowered $ErbB_2$ and $ErbB_3$ protein as well as mRNA expression. In addition, protein and mRNA expression of phosphorylated Akt and total Akt were significantly decreased (p<0.05). We suggest that EGCG inhibits cell proliferation through $ErbB_2$, $ErbB_3$ and Akt cell signaling.

• 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.

• 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.