• Molecules and Cells
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• v.40 no.1
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• pp.54-65
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• 2017

Although cancer/testis antigen DDX53 confers anti-cancer drug-resistance, the effect of DDX53 on cancer stem cell-like properties and autophagy remains unknown. MDA-MB-231 ($CD133^+$) cells showed higher expression of DDX53, SOX-2, NANOG and MDR1 than MDA-MB-231 ($CD133^-$). DDX53 increased in vitro self-renewal activity of MCF-7 while decreasing expression of DDX53 by siRNA lowered in vitro self-renewal activity of MDA-MB-231. DDX53 showed an interaction with EGFR and binding to the promoter sequences of EGFR. DDX53 induced resistance to anti-cancer drugs in MCF-7 cells while decreased expression of DDX53 by siRNA increased the sensitivity of MDA-MB-231 to anti-cancer drugs. Negative regulators of DDX53, such as miR-200b and miR-217, increased the sensitivity of MDA-MB-231 to anti-cancer drugs. MDA-MB-231 showed higher expression of autophagy marker proteins such as ATG-5, $pBeclin1^{Ser15}$ and LC-3I/II compared with MCF-7. DDX53 regulated the expression of marker proteins of autophagy in MCF-7 and MDA-MB-231 cells. miR-200b and miR-217 negatively regulated the expression of autophagy marker proteins. Chromatin immunoprecipitation assays showed the direct regulation of ATG-5. The decreased expression of ATG-5 by siRNA increased the sensitivity to anti-cancer drugs in MDA-MB-231 cells. In conclusion, DDX53 promotes stem cell-like properties, autophagy, and confers resistance to anti-cancer drugs in breast cancer cells.

• Journal of Nutrition and Health
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• v.39 no.8
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• pp.756-761
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• 2006

Curcumin has been known for its anti-proliferative and apoptotic effects on several cancer cells. We examined the inhibitory effects of curcumin on cancer cell adhesion, motility, invasion and matrix metalloproteinase-9 (MMP-9) activity in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured with 0, 5, 10 or $20{\mu}M$ of curcumin. Curcumin significantly inhibited the adhesion of cancer cells to the fibronectin at $20{\mu}M$ and suppressed the motility and invasion of cancer cells at all concentrations. Also, the MMP-9 activity was inhibited by curcumin, but MMP-9 protein amounts were not affected. Our data indicate that curcumin inhibits motility, invasion and MMP-9 activity of MDA-MB-231 cells. Therefore, curcumin may contribute to the potential beneficial food component to prevent the cancer metastasis in human breast cancer.

• Journal of Microbiology and Biotechnology
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• v.19 no.6
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• pp.629-633
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• 2009

The present study investigated the antimetastatic property of chitosan oligosaccharides (COS) by evaluating motility, invasion, and the amount and activity of MMP-9 in MDA-MB-231 human breast carcinoma cells. Treatment of MDA-MB-231 cells with increasing concentrations of COS led to a concentration-dependent decrease in cell migration. COS significantly inhibited the invasion of MDA-MB-231 cells through a Matrigel-coated membrane. The treatment of MDA-MB-231 cells with COS reduced the amounts of secreted MMP-9. The activity and amount of MMP-9 protein in MDA-MB-231 cells were decreased by treatment with COS and occurred in a concentration-dependent manner. Our data indicated that COS can serve as a potential novel therapeutic candidate for the treatment of metastatic breast cancer.

• 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.

• 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.26 no.3
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• pp.44-58
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• 2013

Objectives: Breast cancer is the most common cancer among women and has rapidly increasing rate annually. At present, western cancer therapies by surgery, radiation, and anticancer drug have not been fully effective. So many interests are given to herbal medicine on cancer treatment recently. This study was designed to investigate the effects of Curcuma longa L. (CL) on MDA-MB-231 human breast cancer cells and DMBA-induced breast cancer in rats. Methods: In this experiment, MDA-MB-231 cells were cultured in cell culture plates. 0.0625, 0.125, 0.25, 0.5, 1.0 mg/ml of CL extract were tested for their anti-proliferative effects on MDA-MB-231 cells by MMT assay. And we induced breast cancer in rats. The changes in tumor's weight, and the effects on proliferations of splenocyte and thymocyte were investigated. Results: CL showed anti-proliferative effects on MDA-MB-231 cells in proportion to concentration of the CL. DMBA-induced breast cancer in rats, tumor's weight of the rat was not statistically significant, but showed a tendency to be reduced in the groups treated with CL. Proliferation rate of the rat's splenocyte and thymocyte increased in proportion to CL. In breast cancer tissue, expression of ER-${\alpha}$ was weakened proportionately to the concentration of the CL. Conclusions: These data suggest that CL can prevent the proliferation of breast cancer, then CL is useful to treat patient with breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.5023-5028
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• 2014

Sendai virus strain Tianjin is a novel genotype. Here, we investigate the antitumor and proapoptotic effects of ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) on human breast cancer MDA-MB-231 cells in vitro, as well as the involvement of the apoptotic pathway in the mechanism of UV-Tianjin-induced antitumor effects. MTT assays showed that treatment with UV-Tianjin dose-dependently inhibited the proliferation of MDA-MB-231 cells but not normal MCF 10A breast epithelium cells. Hoechst staining and flow cytometric analysis revealed that UV-Tianjin induced apoptosis of MDA-MB-231 cells in a dose-dependent manner. Moreover, UV-Tianjin treatment resulted in reduction in the mitochondria membrane potential (MMP) and release of cytochrome complex (cyt c) via regulation of Bax and Bcl-2, as well as activation of caspase-9, caspase-3, Fas, FasL and caspase-8 in MDA-MB-231 cells. In summary, our study suggests that UV-Tianjin exhibits anticancer activity in human breast cancer MDA-MB-231 cells through inducing apoptosis, which may involve both the endogenous mitochondrial and exogenous death receptor pathways.

• 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.

• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.129-135
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• 2014

Previously, we reported that lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, can increase intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) via type 1 lysophosphatidic acid (LPA) receptor ($LPA_1$) and CD97, an adhesion G-protein-coupled receptor (GPCR), in MDA-MB-231 breast cancer cells. Furthermore, LPE signaling was suggested as like $LPA_1/CD97-G_{i/o}$ proteins-phospholipase $C-IP_3-Ca^{2+}$ increase in these cells. In the present study, we further investigated actions of LPE not only in the $[Ca^{2+}]_i$ increasing effect but also in cell proliferation and migration in MDA-MB-231 breast cancer cells. We utilized chemically different LPEs and a specific inhibitor of $LPA_1$, AM-095 in comparison with responses in SK-OV3 ovarian cancer cells. It was found that LPE-induced $Ca^{2+}$ response in MDA-MB-231 cells was evoked in a different manner to that in SK-OV3 cells in terms of structural requirements. AM-095 inhibited LPE-induced $Ca^{2+}$ response and cell proliferation in MDA-MB-231 cells, but not in SK-OV3 cells, supporting $LPA_1$ involvement only in MDA-MB-231 cells. LPA had significant effects on cell proliferation and migration in MDA-MB-231 cells, whereas LPE had less or no significant effect. However, LPE modulations of MAPKs (ERK1/2, JNK and p38 MAPK) was not different to those by LPA in the cells. These data support the involvement of LPA1 in LPE-induced $Ca^{2+}$ response and cell proliferation in breast MDA-MB-231 cells but unknown GPCRs (not $LPA_1$) in LPE-induced responses in SK-OV3 cells. Furthermore, although LPE and LPA utilized $LPA_1$, LPA utilized more signaling cascades than LPE, resulting in stronger responses by LPA in proliferation and migration than LPE in MDA-MB-231 cells.