• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.5
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• pp.584-590
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• 2012

Dried $Compositae$ flowers have traditionally been used for the treatment of anti-inflammatory and anti-oxidative stress in Korea. This paper investigates the effects of $Compositae$ extracts on the inhibition of proliferation and apoptosis of human gastric cancer AGS cells, human breast cancer MDA-MB-231 cells, and SK-BR-3 cells. The proliferation of AGS cells, MDA-MB-231 cells, and SK-BR-3 cells were determined by MTT assay. Several $Compositae$ extracts inhibited proliferation of AGS cells, MDA-MB-231 cells, and SK-BR-3 cells in a dose-dependent manner. To assess the apoptosis of $Compositae$ extracts, the nuclei of MDA-MB-231 cells were stained with DAPI. The presence of chromatin condensation in the $Compositae$ extract-treated cells was detected on a fluorescent microscope (${\times}200$). We conducted Western blot analysis of changes in Bcl-2, Bax, and p53 protein expression levels. Apoptosis by $Chrysanthemum$ $zawadskii$ subsp. coreanum, $Chrysanthemum$ $zawadskii$ var. $tenuisectum$ and $Rudbeckia$ $laciniata$ var. $hortensis$ treatment created a decrease in Bcl-2 expression, whereas the expression of Bax and p53 were increased. These results indicate that $Chrysanthemum$ $zawadskii$ $subsp.$ $coreanum$, $Chrysanthemum$ $zawadskii$ var. $tenuisectum$ and $Rudbeckia$ $laciniata$ var. $hortensis$ inhibit breast cancer cell growth through the induction of apoptosis.

• Journal of Life Science
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• v.29 no.4
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• pp.410-420
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• 2019

Citrus unshiu peel extracts possess a variety of beneficial effects, and studies on their anticancer activity have been reported. However, the exact mechanisms underlying this activity remain unclear. In the current study, the apoptotic effect of ethanol extract of C. unshiu peel (EECU) on human breast adenocarcinoma MDA-MB-231 cells and related mechanisms were investigated. The results showed that the survival rate of MDA-MB-231 cells treated with EECU was significantly inhibited in a concentration-dependent manner, which was associated with the induction of apoptosis. EECU-induced apoptosis was associated with the activation of caspase-8 and caspase-9, which initiate extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3, a representative effect caspase. EECU suppressed the expression of the inhibitor of apoptosis family of proteins, leading to an increased Bax/Bcl-2 ratio and proteolytic degradation of poly (ADP-ribose) polymerase. EECU also enhanced the loss of the mitochondrial membrane potential and cytochrome c release from the mitochondria to the cytosol, along with truncation of Bid. In addition, EECU activated AMP-activated protein kinase (AMPK), and compound C, an AMPK inhibitor, significantly weakened EECU-induced apoptosis and cell viability reduction. Furthermore, EECU promoted the generation of reactive oxygen species (ROS), which acted as upstream signals for AMPK activation as pretreatment of cells, with the antioxidant N-acetyl cysteine reversing both EECU-induced AMPK activation and apoptosis. Collectively, these findings suggest that EECU inhibits MDA-MB-231 adenocarcinoma cell proliferation by activating intrinsic and extrinsic apoptotic pathways, which was mediated through ROS/AMPK-dependent pathways.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.272.1-272.1
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• 2003

Cornis fructus were extracted by successive extraction and then fractionated with hexane extract to get active fractions. This study was performed to determine the cytotoxic effect of hexane extract from Cornis fructus on NIH 3T3 fibroblasts and cancer cell lines using MTT assay. Hexane extract showed cytotoxic effect against A549, B16 melanoma and MDA-MB-231. Further fractionation with hexane extract were performed to obtain effective fraction, fraction 3 showed the cytotoxic effect against A549 and MDA-MB-231 cell line.

• Journal of the East Asian Society of Dietary Life
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• v.24 no.6
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• pp.739-747
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• 2014

The aim of the study was to determine the effects of Ixeris dentata extract (IDE) on anticancer activity in human breast cancer MDA-MB-231 cells at both cellular and molecular levels. The cells were cultured in the presence of 0, 20, 30 and $40{\mu}g/mL$ Ixeris dentata extract for 24 hours, respectively. At the end of culture, cytochemical analyses for MTT activity, trypan blue dye exclusion, Annexin V-FITC Apoptosis, and radical oxygen species (ROS) were conducted. RT-PCR was also performed to determine whether or not alterations in cell viability affect the Bax/Bcl-2 ratio. MTT assay showed that relative cell viability decreased in a dose-dependent manner (p<0.05). Reduction of cell viability matched well with increased cell membrane permeability as determined by trypan blue dye exclusion test (p<0.05). The rates of intracellular ROS also increased in a similar manner to those of TB-stained cells. There was an associated shift of apoptotic cells from early to late apoptosis between the 30 and $40{\mu}g/mL$. Bax/Bcl-2 ratio significantly increased along with significant decreases in Bcl-2 expression between 30 and $40{\mu}g/mL$ groups (p<0.05). In conclusion, anticancer activity of Ixeris dentata extract is modulated by a reduction in cell viability along with increased membrane permeability, leading to ROS accumulation within cells, and subsequently cell death through an apoptotic pathway that involves Bax and Bcl-2 in human breast cancer MDA-MB-231 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3071-3075
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• 2016

Morin, a flavonoid found in figs and other Moraceae species, displays a variety of biological actions, exerting anti-oxidant, anti-inflammatory and anti-carcinogenic effects. Here, we investigated the anti-cancer activity of morin focusing on anti-adhesive influence. We performed experiments with MDA-MB-231 human breast cancer cells. Morin inhibited TNF-induced cancer cell adhesion to human umbilical vein endothelial cells (HUVECs) without showing any toxicity. It further inhibited the expression of VCAM-1 on MDA-MB-231 cells as well as HUVECs. Morin also decreased the expression of N-cadherin on MDA-MB-231 cells. In addition, there was apparent anti-metastatic activity in vivo. In conclusion, this study suggested that morin inhibits cancer cell adhesion to HUVECs by reducing VCAM-1, and EMT by targeting N-cadherin, and that it features anti-metastatic activity in vivo. Further investigation of possible anti-metastatic activity of morin against human breast cancer cells is warranted.

• Natural Product Sciences
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• v.23 no.1
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• pp.35-39
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• 2017

D-chiro-inositol (DCI) is a secondary messenger in insulin signal transduction. It is produced in vivo from myo-inositol via action of epimerase. In this study, we evaluated antitumor activity of DCI against human breast cancer both in vitro and in vivo. In order to determine the inhibitory effects of DCI on growth of human breast cancer cells (MDA-MB-231), two different assessment methods were implemented: MTT assay and mouse xenograft assay. MTT assay demonstrated downturn in cell proliferation by DCI treatment (1, 5, 10, 20 and 40 mM) groups by 18.3% (p < 0.05), 17.2% (p < 0.05), 17.5% (p < 0.05), 18.4% (p < 0.05), and 24.9% (p < 0.01), respectively. Also, inhibition of tumor growth was investigated in mouse xenograft model. DCI was administered orally at the dose of 500 mg/kg and 1000 mg/kg body weight to treat nude mouse for 45 consecutive days. On the 45th day, tumor growth of DCI (500 mg/kg and 1000 mg/kg) groups was suppressed by 22.1% and 67.6% as mean tumor volumes were $9313.8{\pm}474.1mm^3$ and $3879.1{\pm}1044.1mm^3$, respectively. Furthermore, breast cancer stem cell (CSC) phenotype ($CD44^+/C24^-$) was measured using flow cytometry. On the 46th day, CSC ratios of DCI (500 mg/kg) and co-treatment with doxorubicin (4 mg/kg) and DCI (500 mg/kg) group decreased by 24.7% and 53.9% (p < 0.01), respectively. Finally, from tumor recurrence assay, delay of 5 days in the co-treatment group compared to doxorubicin (4 mg/kg) alone group was observed. Based on these findings, we propose that DCI holds potential as an anti-cancer drug for treatment of breast cancer.

• BMB Reports
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• v.52 no.3
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• pp.214-219
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• 2019

The role of tumor-proximal factors in tumor plasticity during chemoresistance and metastasis following chemotherapy is well studied. However, the role of endothelial cell (EC) derived paracrine factors in tumor plasticity, their effect on chemotherapeutic outcome, and the mechanism by which these paracrine factors modulate the tumor microenvironment are not well understood. In this study, we report a novel mechanism by which endothelial miR-125a and let-7e-mediated regulation of interleukin-6 (IL-6) signaling can manipulate vasculogenic mimicry (VM) formation of MDA-MB-231 breast cancer cells. We found that endothelial IL-6 levels were significantly higher in response to cisplatin treatment, whereas levels of IL-6 upon cisplatin exposure remained unchanged in MDA-MB-231 breast cancer cells. We additionally found an inverse correlation between IL-6 and miR-125a/let-7e expression levels in cisplatin treated ECs. Interestingly, IL-6, IL-6 receptor (IL-6R), and signal transducer and activator of transcription 3 (STAT3) genes in the IL-6 pathway are closely regulated by miR-125a and let-7e, which directly target its 3' untranslated region. Functional analyses revealed that endothelial miR-125a and let-7e inhibit IL-6-induced adhesion of monocytes to ECs. Furthermore, conditioned medium from cisplatin treated ECs induced a significantly higher formation of VM in MDA-MB-231 breast cancer cells as compared to that from intact ECs; this effect of cisplatin treatment was abrogated by concurrent overexpression of miR-125a and let-7e. Overall, this study reveals a novel EC-tumor cell crosstalk mediated by the endothelial miR-125a/let-7e-IL-6 signaling axis, which might improve chemosensitivity and provide potential therapeutic targets for the treatment of cancer.

• Journal of Life Science
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• v.26 no.11
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• pp.1320-1329
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• 2016

The present study examined the cytotoxic effects of 1, 2, 3, 4, 6-penta-O-galloyl-${\beta}$-D-glucose (PGG), known as the pentahydroxy gallic acid ester of glucose, in the various human cancer cell lines (A-549, MDA-MB-231, U87-MG, MCF-7 and PANC-1), normal MRC-5 fetal fibroblasts, and dental papilla tissue- derived mesenchymal stem cells (DPSCs). Significantly (p<0.05) lower half maximal inhibitory concentration ($IC_{50}$) values were observed in the A-549 and MDA-MB-231 cells showing a high proliferation capacity, compared with other cancer and normal cell lines with a relatively low proliferation capacity. The population doubling time (PDT) was significantly (p<0.05) higher in the $10{\mu}M$ PGG-treated cell lines than those of untreated control cell lines. The present study demonstrated that the $IC_{50}$ value increases proportionally to the extending PDT. A high cell number with senescence-associated ${\beta}-galactosidase$ activity was also observed in the $10{\mu}M$ PGG-treated cells compared with those of untreated control cells. Moreover, the level of telomerase activity was significantly (p<0.05) decreased with $10{\mu}M$ PGG treatment, especially in A-549 and MDA-MB-231 cells showing a high proliferation capacity. Based on these observations, PGG could serve as a potent agent for cancer chemotherapy, as its treatment was more effective in cells with a high proliferation capacity.

• Journal of Life Science
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• v.16 no.4
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• pp.598-604
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• 2006

The $Ca^{2+}-activated$ neutral protease calpain induced proteolysis has been suggested to play a role in certain cell growth regulatory proteins. Cyclin proteolysis is essential for cell cycle progression. D-type cyclins, which form an assembly with cyclin-dependent kinases (cdk4 and cdk6), are synthesized earlier in G1 of the cell cycle and seem to be induced in response to external signals that promote entry into the cell cycle. Here we show that cyclin D3 protein levels are regulated at the posttranscriptional level by calpain protease. Treatment of human breast carcinoma MDA-MB-231 cells with lovastatin and actinomycin D resulted in a loss of cyclin D3 protein that was completely reversible by the peptide aldehyde calpain inhibitor, LLnL. The specific inhibitor of the 26S proteasome, lactacystin, the lysosome inhibitors, ammonium chloride and chloroquine, and the serine protease inhibitor, phenylmethylsulfonylfluoride (PMSF), did not block the degradation of cyclin D3 by lovastatin and actinomycin D. Results of in vitro degradation of cyclin D3 by purified calpain showed that cyclin D3 protein is degraded in a $Ca^{2+}-dependent$ manner, and the half-life of cyclin D3 protein was dramatically increased in LLnL treated cells. These data suggested that cyclin D3 protein is regulated by the $Ca^{2+}-activated$ protease calpain.

• Biomolecules & Therapeutics
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• v.26 no.3
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• pp.322-327
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• 2018

A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.