• BMB Reports
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• v.46 no.1
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• pp.59-64
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• 2013

Signal transducer and activator of transcription 3 (STAT3) and telomerase are considered attractive targets for anticancer therapy. The in vitro anticancer activity of the gold(I) compound auranofin was investigated using MDA-MB 231 human breast cancer cells, in which STAT3 is constitutively active. In cell culture, auranofin inhibited growth in a dose-dependent manner, and N-acetyl-L-cysteine (NAC), a scavenger of reactive oxygen species (ROS), markedly blocked the effect of auranofin. Incorporation of 5-bromo-2'-deoxyuridine into DNA and anchorage-independent cell growth on soft agar were decreased by auranofin treatment. STAT3 phosphorylation and telomerase activity were also attenuated in cells exposed to auranofin, but NAC pretreatment restored STAT3 phosphorylation and telomerase activity in these cells. These findings indicate that auranofin exerts in vitro antitumor effects in MDA-MB 231 cells and its activity involves inhibition of STAT3 and telomerase. Thus, auranofin shows potential as a novel anticancer drug that targets STAT3 and telomerase.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6761-6767
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• 2013

The nuclear receptor, peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$), is expressed in various cancer cells including breast, prostate, colorectal and cervical examples. An endogenous ligand of $PPAR{\gamma}$, 15-deoxy-${\Delta}^{12,14}$ prostaglandin $J_2$ (PGJ2), is emerging as a potent anticancer agent but the exact mechanism has not been fully elucidated, especially in breast cancer. The present study compared the anticancer effects of PGJ2 on estrogen receptor alpha ($ER{\alpha}$)-positive (MCF-7) and $ER{\alpha}$-negative (MDA-MB-231) human breast cancer cells. Based on the reported signalling cross-talk between $ER{\alpha}$ and $ER{\alpha}$, the effect of the $ER{\alpha}$ ligand, $17{\beta}$-estradiol (E2) on the anticancer activities of PGJ2 in both types of cells was also explored. Here we report that PGJ2 inhibited proliferation of both MCF-7 and MDA-MB-231 cells by inducing apoptotic cell death with active involvement of mitochondria. The presence of E2 potentiated PGJ2-induced apoptosis in MCF-7, but not in MDA-MB-231 cells. The $ER{\alpha}$ antagonist, GW9662, failed to block PGJ2-induced activities but potentiated its effects in MCF-7 cells, instead. Interestingly, GW9662 also proved capable of inducing apoptotic cell death. It can be concluded that E2 enhances $ER{\alpha}$-independent anticancer effects of PGJ2 in the presence of its receptor.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2385-2392
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• 2012

The lack of effective treatment targets for triple-negative breast cancers make them unfitted for endocrine or HER2 targeted therapy, and their prognosis is poor. Transcription factor ER81, a downstream gene of the HER2, is highly expressed in breast cancer lines, breast atypical hyperplasia and primary breast cancers including triple-negative examples. However, whether and how ER81 affects breast cancer carcinogenesis have remained elusive. We here assessed influence on a triple-negative cell line. ER81-shRNA was employed to silence ER81 expression in the MDA-MB-231 cell line, and MTT, colony-forming assays, and flow cytometry were used to detect cell proliferation, colony-forming capability, cell cycle distribution, and cell apoptosis in vitro. MDA-MB-231 cells stably transfected with ER81-shRNA were inoculated into nude mice, and growth inhibition of the cells was observed in vivo. We found that ER81 mRNA and protein expression in MDA-MB-231 cells was noticeably reduced by ER81-shRNA, and that cell proliferation and clonality were decreased significantly. ER81-shRNA further increased cell apoptosis and the residence time in $G_0/G_1$ phase, while delaying tumor-formation and growth rate in nude mice. It is concluded that ER81 may play an important role in the progression of breast cancer and may be a potentially valuable target for therapy, especially for triple negative breast cancer.

• Nutrition Research and Practice
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• v.10 no.2
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• pp.139-147
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• 2016

BACKGROUND/OBJECFTIVES: The present study was conducted to examine the inhibitory effect of loquat leaves on MDA-MB-231 cell proliferation and invasion. MATERIALS/METHODS: Female athymic nude mice were given a subcutaneous (s.c.) inoculation of MDA-MB-231 cells and randomly grouped to receive a s.c. injection of either 500 mg/kg ethanol, water extract or vehicle five times a week. Tumor growth, mitotic rate and necrosis were examined. MDA-MB-231 cells were cultured with DMSO or with various concentrations of loquat water or ethanol extract. Proliferation, adhesion, migration, invasion and matrix metalloproteinase (MMP) activity were examined. RESULTS: Tumor growth of xenograft nude mouse was significantly reduced by loquat extracts. The results of mitotic examination revealed that loquat extracts reduced tumor cell division. Both ethanol and water extracts significantly inhibited MDA-MB-231 cell proliferation. The protein expression of ErbB3 was significantly down-regulated by loquat leaf extracts. Loquat leaf extracts increased apoptosis of MDA-MB-231 cells following 24 hour incubation and the ethanol extract was more potent in inducing apoptosis than the water extract. Furthermore, loquat extracts inhibited adhesion, migration and invasion of MDA-MB-231 cells. MMP activity was significantly inhibited by loquat extracts. CONCLUSION: Our results show that extracts of loquat inhibit the growth of tumor in MDA-MB-231 xenograft nude mice and the invasion of human breast cancer cells, indicating the inhibition of tumor cell proliferation and invasion.

• 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.

• 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.

• 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.

• Journal of Life Science
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• v.33 no.1
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• pp.15-24
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• 2023

To examine the antitumor effect of proso millet grains, whether proso millet grains exert apoptotic activity against human cancer cells was investigated. When the cytotoxicity of 80% ethanol (EtOH) extract of proso millet grains was tested against various cancer cells using MTT assay, more potent cytotoxicity was observed against human breast cancer MDA-MB-231 cells than against other cancer cells. When the EtOH extract was evaporated to dryness, dissolved in water, and then further fractionated by sequential extraction using four organic solvents (n-hexane, methylene chloride, ethyl acetate, and n-butanol), the BuOH fraction exhibited the highest cytotoxicity against MDA-MB-231 cells. Along with the cytotoxicity, TUNEL-positive apoptotic nucleosomal DNA fragmentation and several apoptotic responses including BAK/BAX activation, mitochondria membrane potential (Δψm) loss, mitochondrial cytochrome c release into the cytosol, activation of caspase-8/-9/-3, and degradation of poly (ADP-ribose) polymerase (PARP) were detected. However, human normal mammary epithelial MCF-10A cells exhibited a significantly lesser extent of sensitivity compared to malignant MDA-MB-231 cells. Irrespective of Fas-associated death domain (FADD)-deficiency or caspase-8-deficiency, human T acute lymphoblastic leukemia Jurkat cells displayed similar sensitivities to the cytotoxicity of BuOH fraction, excluding an involvement of extrinsic apoptotic mechanism in the apoptosis induction. These results demonstrate that the cytotoxicity of BuOH fraction from proso millet grains against human breast cancer MDA-MB-231 cells is attributable to intrinsic apoptotic cell death resulting from BAK/BAX activation, and subsequent mediation of mitochondrial damage-dependent activation of caspase cascade.

• Journal of the East Asian Society of Dietary Life
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• v.21 no.1
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• pp.24-30
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• 2011

The anti-cancer effects of Angelica keiskei ethanol extract were evaluated in human breast cancer MDA-MB-231 cells. The concentrations of extract were 1, 2, 3, 4 and 5 mg/mL. Dose-dependent reductions in the number of cells with altered cell shape and pyknotic nuclei were observed at 48 h after treatments. MTT assay also exhibited a similar dose-dependent reduction in mitochondrial reductase activity (p<0.05), in particular, with a rapid reduction in the activity of the 5 mg/mL group. Analysis of cell death with propidium iodide (PI) staining revealed only a slight increase in cell death in the 5 mg/mL group. Analysis of bromodeoxyuridine (BrdU) incorporations also showed a dose-dependent reduction in cell proliferation (p<0.05). Finally, increases in total radical oxygen species (ROS) accumulation in cells, as revealed by DCF-DA staining, were observed in the treated groups in a similar dose-dependent fashion (p<0.05). These results indicate that Angelica keiskei ethanol extract exhibiting anti-cancer effects in MDA-MB-231 cells causes multiple changes in cell shape, enzyme activity, and ROS accumulation, thereby inducing cell death.

• Nutrition Research and Practice
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• v.3 no.2
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• pp.77-83
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• 2009

Retinoic acids (RAs) modulate growth, differentiation, and apoptosis in normal, pre-malignant & malignant cells. In the present study, the effects of RA isomers (all-trans RA, 13-cis RA, and 9-cis RA) on the cell signal transduction of human breast cancer cells have been studied. The relationship between RAs and an enzymatic antioxidant system was also determined. Estrogen-receptor (ER) positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells were treated with different doses of each RA isomers, all-trans RA, 13-cis RA, or 9-cis RA. Treatment of RA isomers inhibited cell viability and induced apoptosis of MCF-7 cells as a result of increased caspase activity in cytoplasm and cytochrome C released from mitochondria. All-trans RA was the most effective RA isomer in both cell growth inhibition and induction of apoptosis in MCF-7 cells. However, no significant effect of RA isomers was observed on the cell growth or apoptosis in ER-negative MDA-MB-231 cells. In addition, activities of antioxidant enzymes such as catalase and glutathione peroxidase were decreased effectively after treatment of RA in MCF-7 cells, whereas SOD activity was rarely affected. Thus, the present data suggest that all-trans RA is the most potential inducer of apoptosis and modulator of antioxidant enzymes among RA isomers in MCF-7 human breast cancer cells.