• The Journal of Internal Korean Medicine
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• v.38 no.4
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• pp.409-418
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• 2017

In Korea, Rhus verniciflua Stokes is used to purge hardness, alleviate blood stasis, and treat cancer. However, the mechanisms of related anti-cancer activity are not fully understood in human cancer cells. This study investigated the anti-cancer effects and mechanisms of Rhus verniciflua Stokes on MDA-MB-231 human breast cancer cells and found that treatment with a Rhus verniciflua Stokes extract resulted in time- and concentration-responses that indicated growth inhibition of breast cancer cells by induced apoptosis. This was followed by a decrease in mitochondrial membrane potential; the activation of caspase-3, -8, and -9; and the up-regulation of tBid. Caspase-dependent apoptosis was induced through the inhibition of phosphatidylinositol 3-kinase (PI3K) and the Akt signaling pathway. This study provides evidence that Rhus verniciflua Stokes might be useful for the treatment of breast cancer.

• 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.

• 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.

• Journal of Food Hygiene and Safety
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• v.31 no.1
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• pp.51-58
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• 2016

This research examined the effects of Compositae extract on the inhibition of proliferation and apoptosis in human breast and human gastric cancer cells. Compositae extracts which is used in the experiment are Taraxacum coreanum (TC), Youngia sonchifolia (YS) and Ixeris dentata (ID). The proliferation of SK-BR-3, MDA-MB-231 and AGS cells were investigated by MTT assay. ID and YS extracts inhibited proliferation of SK-BR-3, MDA-MB-231 and AGS cells in a dose-dependent manner, but TC have barely affected. In addition, the most effective extract was ID. To assess the apoptosis of ID extract, the nuclei of human cancer cells were stained with DAPI solution respectively. Chromatin condensation, indicated apoptosis, was increased in a dose-dependent manner. We investigated change of ID extract-induced apoptosis proteins on human cancer cells by western blot analysis. The level of Bcl-2 decreased, whereas the level of Bax, cleaved-PARP increased in dose-dependent manner compared with non-treatment. Also Bax/Bcl-2 ratio, which is used in clinical indicator of apoptosis, was increased at ID extract treatment group compared with non-treatment. Moreover the Bax/Bcl-2 ratio of MDA-MB-231 cell was significantly increased as against SK-BR-3, AGS cells. These results indicated that ID extract have anti-proliferation effect better than YS or TC, and induced apoptosis in human breast cancer MDA-MB-231 cell better than human breast cancer SK-BR-3 cell, human gastric cancer. Even if further research is needed, ID can be developed as a chemopreventive or therapeutic agent of breast cancer.

• Korean Journal of Food Science and Technology
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• v.43 no.2
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• pp.213-219
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• 2011

The metastatic effect of Eupatorium japonicum extract (EJE) on MDA-MB-231 human breast cancer cells was investigated. MDA-MB-231 cells were treated with various concentrations of EJE (0, 5, 10 and $20{\mu}g/mL$). EJE inhibited cell migration, invasion and adhesion of MDA-MB-231 cells in dose-dependent manners. Gelatin zymography exhibited that EJE significantly down regulated secretion of matrix metalloproteinase (MMP)-9 and MMP-2. EJE decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels. Additionally, EJE reduced the protein and mRNA levels of urokinase-type plasminogen activator (uPA), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM). In several solvent fractions of EJE, the hexane fraction markedly decreased MDAMB-231 cell migration. Thus, these finding suggest that EJE may be a potential antimetastatic agent, which can considerably inhibit the metastatic and invasive capacity of breast cancer cells.

• Journal of Applied Biological Chemistry
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• v.52 no.3
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• pp.103-108
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• 2009

Little is known about roles of adipose tissue, although obesity is one of the potential risk factors in causing breast cancer and adipose tissue surrounding breast ductal cells is the largest organ. To identify the genes that are regulated by factors secreted from adipocytes in breast cancer cells, MDA-MB-231 cells were treated with the culture medium of adipocytes. In present study glucocorticoid-induced TNF receptor-related protein ligand (GITRL) gene was studied among the induced genes. It was found that GITRL was significantly increased by the culture medium of adipocytes. Proteinase K-treated adipocyte culture supernatants failed to induce GITRL expression. These findings indicate that unknown protein factors are responsible for the induction of GITRL expression. The expression of GITRL did not affect the invasive ability of MDA-MB-231 cells, but coculture with NK92 expressing GITR suppressed the invasiveness of MDA-MB-231 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8135-8140
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• 2016

Background: Cell cycle regulatory proteins are suitable targets for cancer therapeutic development since genetic alterations in many cancers also affect the functions of these molecules. Strobilanthes crispus (S. crispus) is traditionally known for its potential benefits in treating various ailments. We recently reported that an active sub-fraction of S. crispus leaves (SCS) caused caspase-dependent apoptosis of human breast cancer MCF-7 and MDA-MB-231 cells. Materials and Methods: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle-related transcripts was analysed based on a previous microarray dataset. Results: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of $ER{\alpha}$ protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied. Conclusions: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3211-3217
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• 2014

Background: The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. Materials and Methods: Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose ($D_0$), quasi-threshold dose ($D_q$) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM). Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. Results: The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. Conclusions: Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA-MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.

• 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.

• Korean Journal of Pharmacognosy
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• v.49 no.4
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• pp.285-290
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• 2018

Harmine, a beta-carboline alkaloid isolated from the seeds of Peganum harmala has been reported as a promising drug candidate for cancer therapy. However, the effect of harmine on breast cancer remains still unclear. In this study, the effect of harmine on the cell proliferation, migration, and invasion of breast cancer MDA-MB231 cells and the underlying mechanism were investigated. The results indicated that harmine inhibited the proliferation MDA-MB231 cells in a dose-dependent manner and markedly suppressed migration and invasion of MDA-MB231 cells. The mechanism involved in part through Notch signaling. The Notch activity was significantly inhibited by harmine treatment and harmine suppressed the expression of Jagged1 which is a key ligand to activate Notch signaling. These findings suggest a novel mechanism of harmine on anti-cancer activity and harmine may act as a potential therapeutic drug for breast cancer treatment.