• Korean Journal of Microbiology
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• v.50 no.3
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• pp.261-263
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• 2014

Chronic inflammation is involved in cancers, rheumatoid arthritis, and Crohn's disease. Inerleukin-6 (IL-6) plays major roles in inflammation. Chungkookjang, fermented soybean contains diverse peptides produced by cleavage of soybean proteins. The peptides can be bioactive compounds. Peptide (Gly-Val-Tyr-Tyr-Met-Tyr was purified from Chungkookjang, and modified to be 6mer H, Glu-Val-Tyr-Tyr-Met-Tyr (EVYYMY). Peptide H's activity to suppress IL-6 expression in a human breast cancer cell, MDA-MB-231 was determined. IL-6 Expression was reduced in the cell treated with peptide H 25 times less than controls which were not treated with peptide H. Proliferation of MDA-MB-231 cells was inhibited by peptide H, which is concentration-dependent. Blocking of IL-6 signals is known to be effective in reducing inflammation in rheumatoid arthritis, Crohn's disease, and cancers. Since peptide H can reduce inflammatory IL-6 expression, application of this study will contribute to drug development for diseases which are caused by excessive IL-6.

• 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.

• Korean Journal of Microbiology
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• v.52 no.3
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• pp.380-382
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• 2016

Chungkookjang, fermented soybeans, contains diverse peptides produced during fermentation. Fermented soybean extracts containing the peptides can affect cellular signal transduction. Proliferation of human breast cancer MDA-MB-231 cells were repressed dependent on concentrations of fermented soybean extracts. Since fermented soybean extracts inhibited breast cancer cell's growth, and inflammation is related to cancer, it is determined whether it can suppress inflammatory $TNF{\alpha}$ expression. $TNF{\alpha}$ expression in MDA-MB 231 cells treated with fermented soybean extracts was repressed by that extracts. $TNF{\alpha}$ inhibitors were developed as drugs for autoimmune diseases. Since fermented soybean extracts suppressed $TNF{\alpha}$ expression, it can be developed as those drugs.

• Journal of Nutrition and Health
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• v.41 no.8
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• pp.711-717
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• 2008

Anthocyanidins, the aglycones of anthocyanins, are natural colorants belonging to the flavonoid family. Cyanidin is one of the anthocyanidins, used for their antioxidant properties. Furthermore, previous studies have shown anthocyanidin-rich material extracts or aglycone form inhibit growth and induce apoptosis of cancer cells. But, Tumor metastasis is the most important cause of cancer death, and various treatment strategies have targeted on preventing the occurrence of metastasis. This study investigated the effects of cyanidin on metastasis processes, including motility, invasion and activity of MMP-2 and MMP-9 in MDA-MB-231 human breast cancer cell lines. We cultured MDA-MB-231 cells in presence of various concentrations 0, 5, 10 and 20 ${\mu}M$ of cyanidin. The cell motility was significantly decreased dosedependently in cells treated with cyanidin (p < 0.05) and cyanidin treatment caused the significant suppression of the invasion (p < 0.05). MMP-2 and MMP-9 activities, and MMP-9 mRNA express were not affected by anthocyanin treatment. In conclusion, cyanidin inhibits cell motility, invasion in MDA-MB-231 human breast cancer cell lines.

• Animal cells and systems
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• v.16 no.4
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• pp.274-279
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• 2012

Thymoquinone (TQ), a drug extracted from the black seeds of Nigella sativa, has been shown to exhibit anti-inflammatory, anti-oxidant, and anti-neoplastic effects in numerous cancer cells. The effects of TQ on cyclooxygenase-2 (COX-2) expression and prostaglandin $E_2$ ($PGE_2$) production in MDA-MB-231, however, remain poorly understood. Western blot analysis and immunofluorescence staining were performed to study the expression levels of inflammation regulatory proteins in MDA-MB-231. $PGE_2$ assay was conducted to explore the TQ-induced production of $PGE_2$. In this study, we investigated the effects of TQ on COX-2 expression and $PGE_2$ production in MDA-MB-231. TQ significantly induced COX-2 expression and increased $PGE_2$ production in a dose-dependent manner, as determined by a Western blot analysis and $PGE_2$ assay. Furthermore, the activation of Akt and p38 kinase, respectively, was up-regulated in TQ treated cells. Inhibition of p38 kinase with SB203580 and PI3kinase (PI3K) with LY294002 abolished TQ-caused COX-2 expression and decreased $PGE_2$ production. These results collectively demonstrate that TQ effectively modulates COX-2 expression and $PGE_2$ production via PI3K and p38 kinase pathways in the human breast cancer cell line MDA-MB-231.

• 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.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.591-602
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• 2019

Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231. Although G0S2 acts as a direct inhibitor of adipose triglyceride lipase, action of G0S2 in cancer progression is not yet understood. To investigate whether G0S2 affects invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin-regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. In addition, G0S2 downregulation decreased ${\beta}$-catenin expression, while E-cadherin expression was increased. It was demonstrated for the first time that G0S2 mediates the Hippo pathway and induces epithelial to mesenchymal transition (EMT). Taken together, our results suggest that G0S2 is a major factor contributing to cell survival and metastasis of MDA-MB-231 cells.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.479-488
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• 2021

This study aimed to develop docetaxel (DTX) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (DTX-NPs) and to evaluate the different pharmacological sensitivity of NPs to MCF-7 and MDA-MB-231 breast cancer cells. NPs containing DTX or coumarin-6 were prepared by the nanoprecipitation method using PLGA as a polymer and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a surfactant. The physicochemical properties of NPs were characterized. In vitro anticancer effect and cellular uptake were evaluated in breast cancer cells. The particle size and zeta potential of the DTX-NPs were 160.5 ± 3.0 nm and -26.7 ± 0.46 mV, respectively. The encapsulation efficiency and drug loading were 81.3 ± 1.85% and 10.6 ± 0.24%, respectively. The in vitro release of DTX from the DTX-NPs was sustained at pH 7.4 containing 0.5% Tween 80. The viability of MDA-MB-231 and MCF-7 cells with DTX-NPs was 37.5 ± 0.5% and 30.3 ± 1.13%, respectively. The IC₅₀ values of DTX-NPs were 3.92- and 6.75-fold lower than that of DTX for MDA-MB-231 cells and MCF-7 cells, respectively. The cellular uptake of coumarin-6-loaded PLGA-NPs in MCF-7 cells was significantly higher than that in MDA-MB-231 cells. The pharmacological sensitivity in breast cancer cells was higher on MCF-7 cells than on MDA-MB-231 cells. In conclusion, we successfully developed DTX-NPs that showed a great potential for the controlled release of DTX. DTX-NPs are an effective formulation for improving anticancer effect in breast cancer cells.

• 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 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)