• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10245-10250
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• 2015

Background: Glucocorticoids are commonly co-administered with chemotherapy to prevent drug-induced allergic reactions, nausea, and vomiting, and have anti-tumor functions clinically; however, the distinct effects of GC on subtypes of tumor cells, especially in breast cancer cells, are still not well understood. In this study, we aimed to clarify the effect of GC on subtypes of T47D breast cancer cells by focusing on apoptosis, cell organization and migration, and underluing molecular mechanisms. Materials and Methods: The cell scratch test was performed to observe the cell migration rate in T47D cells treated with dexamethasone (Dex). Hoechst and MTT assays were conducted to detect cell survival and rhodamine-labeled phalloidin staining to observe cytoskeleton dynamics. Related factors in the AKT/mTOR pathway were determined by Western blotting. Results: Dex treatment could effectively inhibit T47D breast cancer cell migration with disruption of the cytoskeletal dynamic organization. Moreover, the effect of Dex on cell migration and cytoskeleton may be mediated by AKT/mTOR/RhoA pathway. Although Dex inhibited T47D cell migration, it alone may not induce cell apoptosis in T47D cells. Conclusions: Dex in T47D human breast cancer cells could effectively inhibit cell migration by disrupting the cytoskeletal dynamic organization, which may be mediated by the AKT/mTOR/RhoA pathway. Our work suggests that glucocorticoid/Dex clinical use may prove helpful for the treatment of breast cancer metastasis.

• Journal of Animal Reproduction and Biotechnology
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• v.38 no.3
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• pp.167-176
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• 2023

Background: A breast cancer is the second leading cause of cancer death in women worldwide and among different types of breast cancers, triple-negative breast cancer (TNBC) has a poor prognosis. Methods: We investigated the potential of ginsenoside compound K (CK), an active ingredient in the bio-transformed ginsenoside, to be used as a therapeutic ingredient by examining the effects of CK on cell proliferation, apoptosis, and cancer-related gene expressions in breast cancer cells. Results: From the results of treating MCF-7, an ER and PR-positive breast cancer cells, and MDA-MB-231 (TNBC) with CK at a concentration of 0-100 µM, the half maximal inhibitory concentration (IC₅₀) values for each cell were 52.17 µM and 29.88 µM, respectively. And also, it was confirmed that cell migration was inhibited above the IC50 concentration. In addition, fluorescence analysis of Apoptosis/Necrosis showed that CK induced apoptosis rather than necrosis of breast cancer cells. Through qPCR, it was confirmed that the expression of genes related to apoptosis and cell cycle arrest was increased in CK-treated breast cancer cells, and it acted more effectively on TNBC. However, the expression of genes related to tumor invasion and metastasis is also increased, so it is necessary to consider the timing of application of CK as a potential therapeutic anticancer compound. Conclusions: CK showed a stronger inhibitory effect in TNBC with poor prognosis but considering the high tumor invasion and metastasis-related gene expression, the timing of application of CK should be considered.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.503-511
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• 2018

Lysophosphatidic acid (LPA) is known to play a critical role in breast cancer metastasis to bone. In this study, we tried to investigate any role of LPA in the regulation of osteoclastogenic cytokines from breast cancer cells and the possibility of these secretory factors in affecting osteoclastogenesis. Effect of secreted cytokines on osteoclastogenesis was analyzed by treating conditioned media from LPA-stimulated breast cancer cells to differentiating osteoclasts. Result demonstrated that IL-8 and IL-11 expression were upregulated in LPA-treated MDA-MB-231 cells. IL-8 was induced in both MDA-MB-231 and MDA-MB-468, however, IL-11 was induced only in MDA-MB-231, suggesting differential LPARs participation in the expression of these cytokines. Expression of IL-8 but not IL-11 was suppressed by inhibitors of PI3K, NF-kB, ROCK and PKC pathways. In the case of PKC activation, it was observed that $PKC{\delta}$ and $PKC{\mu}$ might regulate LPA-induced expression of IL-11 and IL-8, respectively, by using specific PKC subtype inhibitors. Finally, conditioned Medium from LPA-stimulated breast cancer cells induced osteoclastogenesis. In conclusion, LPA induced the expression of osteolytic cytokines (IL-8 and IL-11) in breast cancer cells by involving different LPA receptors. Enhanced expression of IL-8 by LPA may be via ROCK, PKCu, PI3K, and NFkB signaling pathways, while enhanced expression of IL-11 might involve $PKC{\delta}$ signaling pathway. LPA has the ability to enhance breast cancer cells-mediated osteoclastogenesis by inducing the secretion of cytokines such as IL-8 and IL-11.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1877-1880
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• 2012

Breast cancer metastasis is the most common cause of cancer-related death in women. Thus, seeking targets of breast tumor cells is an attractive goal towards improving clinical treatment. The present study showed that CCL18 from tumor-associated macrophages could promote breast cancer metastasis via PITPNM3. In addition, we found that pachymic acid (PA) could dose-dependently inhibit migration and invasion of MDA-MB-231cells, with or without rCCL18 stimulation. Furthermore, evidence was obtained that PA could suppress the phosphorylation of PITPNM3 and the combination of CCL18 and PITPNM3. Therefore, we speculate that PA could inhibit breast cancer metastasis via PITPNM3.

• The Journal of Pediatrics of Korean Medicine
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• v.27 no.1
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• pp.59-68
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• 2013

Objectives The aim of this study is to investigate whether hwang-ryun-haedok-tang (HDT) affect proliferations of androgen-dependent LNCaP prostate cancer cells, androgen-independent PC-3, DU-145 prostate cancer cells, MCF-7 human breast cancer cells, A549, NCI-H292 human pulmonary cancer cells and K-562 human chronic myelogenous leukemia cells. Materials and Methods Effects of HDT on proliferations of each cancer cell line were investigated. 20,000 cells/well were plated in each well of 96-well culture plate. After 24 hrs, 0.01-10% of HDT in culture medium was added to cancer cells. The number of cells was counted by using SRB assay or direct cell counting method after 72 hours from drug treatment. Effect of baicalein or berebrine on proliferation was assessed according to the same method. Results (1) HDT inhibited proliferations of LNCaP, PC-3 and DU-145 prostate cancer cells. (2) HDT inhibited proliferation of MCF-7 breast cancer cells. (3) HDT also inhibited proliferations of A549, NCI-H292 pulmonary cancer cells and K-562 chronic myelogenous leukemia cells. (4) Baicalein and berberine also showed inhibitory effects on proliferations of prostate and breast cancer cells. Conclusion : HDT inhibited proliferations of human prostate, breast, pulmonary and blood cancer cells. These results suggest us the potential use of HDT as a chemopreventive or chemotherapeutic agent. Effect of HDT on human cancer should be further investigated using in vivo experimental models that can reflect pathophysiology of human cancer through another studies.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.87-94
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• 2008

In view of obtaining potential anticancer compounds, we studied the inhibitory activity and the cytotoxic effects of a candidate compound in cancer cells. The cytotoxic effects of cannabidiol (CBD) in vitro were evaluated in NIH3T3 fibroblasts, B16 melanoma cells, A549 lung cancer cells, MDA-MB-231 breast cancer cells, Lenca kidney cells and SNU-C4 colon cancer cells. The cells were cultured in various concentrations of CBD for 48 h and 25 ${\mu}$M of CBD for 6-36 h. The cells were observed to exhibit inhibitory effects of the cell viability in their growth, and then cytotoxicity was estimated. The inhibitory activity of CBD was increased in all cancer cells and showed especially strong increment in breast cancer cells. The cytotoxicity of CBD increased in a dose- and time-dependent manner with growth inhibition in all cancer cell lines. Also, to assess the membrane toxicity induced by CBD, we investigated lactate dehydrogenase (LDH) release. After treatment with various concentrations of CBD, LDH release rate of cancer cells was accelerated. On the other hand, in the induction of cell death, caspase-3, -8 and -9 activations were detected in cancer cells after treatment with various concentrations of CBD, and CBD effectively induced activity of caspase-3, -8 and -9 in A549 lung cancer cells, MDAMB-231 breast cancer cells and Renca kidney cells. Therefore these results suggest that CBD has a possibility of anticancer agents and anticancer effects against cancer cells by modulation of apoptotic pathway in the range of 5-80 ${\mu}$M concentration.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2751-2756
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• 2015

Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can specifically induce apoptosis limited to various cancer cells, so this reagent is considered a promising medicine for cancer therapy. TRAIL also exerts effects on non-apoptotic signals, relevant to processes such as metastasis, autophagy and proliferation in cancer cells. However, the mechanisms of TRAIL-regulated non-apoptotic signals are unclear. The purpose of this study was to investigate MADD/CXCR7 effects in TRAIL-mediated breast cancer cell migration. Materials and Methods: The ability of MADD/CXCR7 to regulate MVP signaling in TRAIL-mediated breast cancer cells migration was evaluated by transwell migration assay, quantitative RT-PCR, Western blotting and knock down experiments. Results: In this study, we found that treatment with TRAIL resulted in induced expression levels of MADD and CXCR7 in breast cancer cells. Knock down of MADD followed by treatment with TRAIL resulted in increased cell migration compared to either treatment alone. Similarly, through overexpression and knockdown experiments, we demonstrated that CXCR7 also positively regulated TRAIL-inhibited migration. Surprisingly, knock down of MADD lead to inhibition of TRAIL-induced CXCR7 mRNA and protein expression and overexpression of CXCR7 lead to the reduction of MADD expression, indicating that MADD is an upstream regulatory factor of TRAIL-triggered CXCR7 production and a negative feedback mechanism between MADD and CXCR7. Furthermore, we showed that CXCR7 is involved in MADD-inhibited migration in breast cancer cells. Conclusions: Our work defined a novel signaling pathway implicated in the control of breast cancer migration.

• The Journal of Korean Obstetrics and Gynecology
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• v.20 no.1
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• pp.32-49
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• 2007

Purpose: Breast cancer is the most common disease in Korean women. Despite remarkable improvements in treatment strategies against various cancer during the past 40 years, breast cancer still remains as one of the main causes of cancer mortality among women in the whole world. This study was carried out to investigate antioxidative and anti-proliferative effects on MCF-7 human breast cancer cells of Ikiyangyoung-Tang extract. Methods: We measured a content of polyphenol and flavonoid in the Ikiyangyoung-Tang extract, eliminative ability of DPPH radical, ABTS free radical and hydrogen peroxide, antioxidative effects of linoleic acid, cytotoxicity on MCF-7 human breast cancer cells. MCF-7 cells were cultured in Dulbecco's modified Eagle's medium/F12(DMEM/F12) supplemented with 10 % fetal bovine serum(FBS; Gibco) and antibiotics. Results : The extract of Ikiyangyoung-Tang contains polyphenol of 168.3${\pm}$12.8 ${\mu}$g/mg and flavonoid of 84.3${\pm}$3.4 ${\mu}$g/mg. Above results show profitable abilities of elimination of ${\alpha}$-${\alpha}$-Diphenyl-${\beta}$-picrylhydrazyl(DPPH) radical, ABTS free radical and hydrogen peroxide. Also, the extract of Ikiyangyoung-Tang strongly inhibits the proliferation of MCF-7 cells in a dose ependent manner. And. it has cytotoxicity on NIH3T3 cells. Conclusion : It can be concluded that Ikiyangyoung-Tang extract has an antioxidative effect and antiproliferative effect on MCF-7 human breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1105-1110
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• 2014

Objective: Metastases and invasion are the main reasons for oncotherapy failure. Momordica cochinchinensis (Mu Bie Zi in Chinese) had been used for a variety of purposes, and shown anti-cancer action. In this article, we focused on effects on regulation of breast cancer cell ZR-75-30 metastases and invasion by extracts of Momordica cochinchinensis seeds (ESMCs). Methods: Effect of ESMCs on ZR-75-30 human breast cancer cells proliferation were evaluated by MTT assay and on invasion and migration by wound-healing and matrigel invasion chamber assays. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. Results: ESMC revealed strong growth inhibitory effects on ZR-75-30 cells, and effectively inhibited ZR-75-30 cell invasion in a dose-dependent manner. Western blot and gelatin zymography analysis showed that ESMC significantly inhibited the expression and secretion of MMP-2 and MMP-9 in ZR-75-30 cells. Conclusions: ESMC has the potential to suppress the migration and invasion of ZR-75-30 cancer cells, and it might prove to of interest in the development of novel inhibitors for breast cancer.

• 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.