• 동의생리병리학회지
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• 제28권3호
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• pp.310-316
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• 2014

Oldenlandia diffusa, Cremastra appendiculata and Fritillaria thunbergii are widely distributed in the Korea, China and Japan, and has been used in traditional medicine for various diseases, such as pharyngolaryngitis, tonsillitis, goiter and stomach ulcer. However, the anti-cancer activities in human breast cancer have not been clearly elucidated yet. In this study, it was compared the in vitro cytotoxic effects of single and complex treatment of O. diffusa, C. appendiculata and F. thunbergii. We treat human breast cancer MCF-7 cells with O. diffusa, C. appendiculata and F. thunbergii. And we evaluated viability, growth inhibition, morphological changes, apoptotic bodies formation, measurement of the cell cycle and formation of DNA fragmentation of these cells. It was found that single treatment of O. diffusa could inhibit the cell proliferation in human breast cancer MCF-7 cells. However, complex treatment of O. diffusa, C. appendiculata and F. thunbergii is weakly or not affect the cell proliferation of MCF-7 cells. And anti-proliferative effects of O. diffusa in MCF-7 cells was associated with G1 arrest of cell cycle. These findings suggest that O. diffusa may be a potential chemotherapeutic agent for the control of human breast cancer cells and further studies will be needed to identify the molecular mechanisms.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1431-1437
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• 2012

The growth of many breast tumors is stimulated by IGF-1, which activates signal transduction pathways inducing cell proliferation. $ER{\alpha}$ is important in this process. The aim of the study was to investigate relationships in vitro among inhibitory effects of luteolin on the growth of MCF-7 cells, IGF-1 pathway and $ER{\alpha}$. Our results showed that luteolin could effectively block IGF-l-stimulated MCF-7 cell proliferation in a dose- and time-dependent manner and block cell cycle progression and induce apoptosis evidenced by the flow cytometric detection of sub-G1DNA content. Luteolin markedly decreased IGF-l-dependent IGF-IR and Akt phosphorylation without affecting Erk1/2 phosphorylation. Further experiments pointed out that $ER{\alpha}$ was directly involved in IGF-l induced cell growth inhibitory effects of luteolin, which significantly decreased $ER{\alpha}$ expression. Knockdown of $ER{\alpha}$ in MCF-7 cells by an $ER{\alpha}$-specific siRNA decreased the IGF-l induced cell growth inhibitory effects of luteolin. $ER{\alpha}$ is thus a possible target of luteolin. These findings indicate that the inhibitory effect of luteolin on the growth of MCF-7 cells is via inhibiting IGF-l mediated PI3K-Akt pathway dependent of $ER{\alpha}$ expression.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.6135-6140
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• 2013

Background: Breast cancer is a common malignant tumor which affects health of women and multidrug resistance (MDR) is one of the main factors leading to failure of chemotherapy. This study was conducted to establish paclitaxel-resistant breast cancer cell line and nude mice models to explore underlying mechanisms of MDR. Methods: The breast cancer drug-sensitive cell line MCF-7 (MCF-7/S) was exposed in stepwise escalating paclitaxel (TAX) to induce a resistant cell line MCF-7/TAX. Cell sensitivity to drugs and growth curves were measured by MTT assay. Changes of cell morphology and ultrastructure were examined by optical and electron microscopy. The cell cycle distribution was determined by flow cytometry. Furthermore, expression of proteins related to breast cancer occurrence and MDR was tested by immunocytochemistry. In Vivo, nude mice were injected with MCF-7/S and MCF-7/TAX cells and weights and tumor sizes were observed after paclitaxel treatment. In addition, proteins involved breast cancer and MDR were detected by immunohistochemistry. Results: Compared to MCF-7/S, MCF-7/TAX cells had a higher resistance to paclitaxel, cross-resistance and prolonged doubling time. Moreover, MCF-7/TAX showed obvious alterations of ultrastructure. Estrogen receptor (ER) expression was low in drug resistant cells and tumors while expression of human epidermal growth factor receptor 2 (HER2) and Ki-67 was up-regulated. P-glycoprotein (P-gp), lung resistance-related protein (LRP) and glutathione-S-transferase-${\pi}$ (GST-${\pi}$) involved in the MDR phenotype of resistant cells and tumors were all overexpressed. Conclusion: The underlying MDR mechanism of breast cancer may involve increased expression of P-gp, LRP and GST-${\pi}$.

• 대한한방내과학회지
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• 제43권4호
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• pp.529-541
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• 2022

Objectives: Acanthopanax senticosus is a tree used in traditional medicine for various diseases. In this study, we investigated the anti-cancer effects of a water extract of Acanthopanax senticocus fruit (ASF) on 2 human breast cancer cell lines (MCF-7 and MDA-MB-231). Methods: The MTT assay was used to assess cell proliferation. The expression of apoptosis-related genes was assessed by quantitative real-time PCR. Results: ASF treatment caused a dose-dependent inhibition of cell growth in both estrogen-independent MDA-MB-231 and estrogen-dependent MCF-7 breast cancer cells. ASF decreased mRNA expression of the apoptotic suppressor gene Bcl-xL, and increased mRNA expression of proapoptotic genes. ASF increased the mRNA expression of p21 and RIP-1 in both cell types. ASF decreased the mRNA expression of survivin in the MCF-7 cell line. Conclusions: ASF exhibits anti-cancer activity involving apoptotic cell death.

• Preventive Nutrition and Food Science
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• 제7권2호
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• pp.128-132
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• 2002

The present study was performed to observe the role of protein kinase C (PKC) inhibitors (H-7, staurosporine) and daunorubicin in the cell death process of MCF7 cells; and examined whether or not the type of induced cell death was apoptosis. The usefulness of the combined therapy of PKC inhibitors and daunorubicin to improve the adverse effect of daunorubicin was also investigated. Cell death was induced by treatment with PKC inhibitors or daunorubicin. Characteristic morphologic features of cell shrinkage, chromatic condensation, and cytoplasmic vacuolization were observed. These treatments also stimulated the cleavage of poly-(ADP-ribose) polymerase (PARP), an early event in apoptosis. With slight differences in the percentage of apoptosis-induced cells, staurosporine, H-7 and daunorubicin effectively induced apoptosis in MCF7 cells. Furthermore, combined treatment of PKC inhibitors and daunorubicin significantly drove the cells into an apoptotic state. Hence, our results revealed the possible therapeutic value of combined therapy for the prevention of drug resistance and adverse side effects.

• 환경생물
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• 제23권1호
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• pp.21-26
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• 2005

Cell response to genotoxic agents is complex and involves the participation of different classes of genes including cell cycle control, DNA repair and apoptosis. In this report, we presented a approach to characterize the cellular functions associated with the altered transcript profiles of MCF-7 exposed to low-dose in vitro gamma-irradiation. We used the method of human 2.4 k cDNA microarrays containing apoptosis, cell cycle, chromatin, repair, stress and chromosome genes to analyze the differential gene expression characterization that were displayed by radiation-exposed cell, human breast carcinoma MCF-7 cell line, such as 4 Gy 4 hr, 8 Gy 4 hr, and 8 Gy 12 hr. Among these genes, 66 were up-regulated and 49 were down-regulated. Specific genes were concomitantly induced in the results. Cyclin dependent kinase 4 (Cdk4) is induced for starting the cell cycle. This regulation is required for a DNA damage­induced G1 arrest. In addition to, an apoptotic pathways gene Bcl-w was concomitantly induced. Mismatch repair protein homologue-l (hMLH1), a necessary component of DNA mismatch protein repair (MMR), in G2-M cell cycle checkpoint arrest. The present study provides new information on the molecular mechanism underlying the cell response to genotoxic stress, with relevance to basic and clinical research.

• 한국환경성돌연변이발암원학회지
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• 제20권1호
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• pp.14-20
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• 2000

DHAQ-97, (2-(3-[p-bis(2-chloroethyl)aminophenyl]-2 formylaminopropanoyloxy) methy1-1,4-dihy-droxy-9,10-anthraquinone), is a novel anthraquinone derivative synthesized for use as an anti-neoplastic agent. In the present study, we have evaluated the selective cytotoxicity of DHAQ-97 by comparing its effects on viability and proliferation of human breast cancer cell line (NCF-7) versus normal immortalized breast epithelial cell line (MCF-10A). Thus, DHAQ-97 reduced both viability and proliferation of MCF-7 cells to a much greater extent than did for MCF-10A cells. The growth inhibitory and anti-proliferative properties of DHAQ-97 appear to be attributable to its ability to induce apoptosis as revealed by positive staining after in 냐셔 nick-end labeling (TUNEL), cleavage of poly(ADP-ribose)polymerase, release of mitochondrial cytochrome c into cytoplasm, and increased expression of pro-apoptotic Bax protein. Recent studies have indicated possible involvement of the ubiquitous eukaryotic transcription factor, NF-kappa B (NF-kB) in the regulation of apoptotic cell death. In line induced cytotoxicity in cultured MCF-7 cells. Furthermore, mild activation of NF-kB, as determined by its increased DNA binding capability, was observed 30 min after treatment with 10$\mu\textrm{m}$ DHAQ-97. Taken together, the above findings suggest that DHAQ-97 exerts selective cytotoxicity towards cancer cells through induction of apoptosis, which appears to be regulated by NF-kB.

• 대한본초학회지
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• 제21권1호
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• pp.57-62
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• 2006

Objectives : This study was carried out to investigate the inhibitive effects of cotton plant sectional extracts in cancer cell lines, Calu-6(human, Caucasian, lung, adenocarcinoma) and MCF-7(human, Caucasian, breast, adenocarcinoma). The incidence of cancer has been increasing even in korea due to the change of dietary life and westernization and becoming conspicuous as the disease threatening health. But cancer treatment have not been fully effective against the high incidence or low survival rate of most cancer. Methods : Calu-6 and MCF-7 cells were cultured and seeded in cell culture plates, respectively. And sectional extracts of cotton plant were treated to MCF-7 cells. Results and Conclusion : Sectional extracts of cotton plant showed no anti-proliferative effect on MCF-7 cells, but root and stem extracts showed strong anti-proliferative effects on Calu-6 cells. Fruit, leaf and flower extracts also showed anti-proliferative effects on Calu-6 cells but not so much like root and stem extracts. But seed extract showed no anti-proliferative effect on Calu-6 cells.

• Molecular & Cellular Toxicology
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• 제2권1호
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• pp.15-20
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• 2006

Genistein is a potent, plant-derived isoflavone that displays estrogenic activity at low concentrations but inhibits proliferation at high amounts. However, the molecular mechanism of genistein is not completely understood. In the present study, the biphasic effects (estrogenic and antiestrogenic activity) of genistein on the growth of MCF-7 cells were identified. Genistein within a low range of concentration, $1-10\;{\mu}M$, stimulated proliferation, while $50-100\;{\mu}M$ caused apoptotic cell death. Additionally, genistein at a low concentration induced estrogen receptor (ER)-mediated gene expression and ER phosphorylation. When pre-treated with PD98059, an MEK inhibitor, ER-mediated gene expression and ER phosphorylation by genistein were noticeably increased. However, the increased gene expression and phosphorylation did not enhance cell proliferation. Moreover, it was observed that ER-mediated signaling performs an important role in the MAPK pathway. The proliferation and apoptosis in genistein-treated MCF-7 cells were partially dependent on the Bcl-2 level. The addition of IC1 182, 780, an estrogen receptor antagonist, inhibited Bcl-2 expression induced by genistein. This study suggests that there is a close relationship between Bcl-2 and the ER signaling pathways in MCF-7 cells.

• International Journal of Oral Biology
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• 제40권4호
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• pp.223-228
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• 2015

6-Gingerol exerts anti-tumor effects in various cancer cell models. We evaluated the effect of 6-gingerol on the growth of MCF-7 breast cancer cells and MCF-10A breast epithelial cells to determine whether any growth-inhibitory effects found were attributable to apoptosis, and to elucidate the underlying mechanism of action. 6-Gingerol inhibited the viability of both cell lines in a dose- and time-dependent manner; however, the degree of inhibition was greater in MCF-7 than MCF-10A cells. By flow cytometry, induction of dose- and time-dependent apoptosis was found, and the magnitude of apoptosis was also markedly greater in MCF-7 than MCF-10A cells. Expression of caspase-3 and poly (ADP-ribose) polymerase (PARP) was observed in MCF-7 cells treated with 6-gingerol, and further cleavage of PARP occurred in these cells. We suggest that 6-gingerol induces apoptosis in human breast cancer cells mainly by promoting caspase-3 expression and subsequent degradation of PARP.