• KSBB Journal
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• v.18 no.5
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• pp.424-428
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• 2003

In the present study, we have analyzed effects of the endocrine distruptors, such as bisphenol A, nonylphenol and pentachlorophenol, on cell proliferation in the human breast cancer cell line, MCF-7, and the human prostate cancer cell line, PC-3, with MTT method. A dose dependent analysis of the cell proliferation of MCF-7 cells after administration of bisphenol A, nonylphenol and pentachlorophenol revealed a significant induction of cell proliferation. Maximum induction of cell proliferation was observed at concentrations between 10$\^$-7/ and 10$\^$-6/ M. Whereas, these chemicals had little effect on proliferation of PC-3 cells. These results demonstrated that bisphenol A, nonylphenol and pentachlorophenol do not induce proliferation of PC-3 cells but exhibit a significant induction of MCF-7 cell proliferation, suggesting all these chemicals are a estrogen mimic.

• Journal of the Korean Society of Tobacco Science
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• v.25 no.2
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• pp.128-136
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• 2003

Although tobacco smoke has been known to have genotoxicity as well as cytotoxicity, the sensitivity of the cell lines used against cigarette smoke is poorly understood. The objective of this study was to evaluate and compare the genotoxicity of several cell lines, which are routinely used in the in vitro assays, with cigarette smoke condensate(CSC) of Kentucky Reference Cigarette 1R4F. In the micronucleus(MN) induction assays, murine(CHO-K1, V79, BALB/c 3T3) cell lines and human(MCF-7, A549) ones were used. As a result, the CSC exhibited cytotoxicity with a concentration-dependent response in all cell lines. EC$_{50}$ of CSC in CHO-K1, V79, BALB/c 3T3, MCF-7 and A549 were 140, 125, 100, 116 and 109 $\mu\textrm{g}$/mL, respectively. On the other hand, the spontaneous micronucleated cell(MNC) frequency was stable and reproducible in every cell lines tested in this study. The dose-response of various cell lines to the induction of MN by CSC was estimated using linear regression analysis. CSC(0～100 $\mu\textrm{g}$/mL) caused a dose-dependent MN induction in CHO-K1, V79, BALB/c 3T3 and MCF-7 cell lines. Putting together all the data obtained and linear regression analysis of the data, we concluded that V79 cells are more susceptible to the accurate assessment of CSC-induced MN than the others.s.

• Journal of Acupuncture Research
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• v.20 no.3
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• pp.45-62
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• 2003

Objective : To examine the effects of Beevenom on the cell proliferation of human breast carcinoma cell line MCF-7, we performed various experiments such as does-dependent effect of Beevenom on cell proliferation and viability, morphological changes, and alterations of apoptosis/cell cycle-regulatory gene products. Methods : Beevenom induced cell viability and proliferation of MCF-7 cells in a concentration-dependent manner. The anti-proliferative effect by Beevenom treatment in MCF-7 cells was associated with morphological changes such as membrance shrinking and cell rounding up. Results : Beevenom induced apoptotic cell death in a concentration-dependent manager, which was associated with degradation of ${\beta}$-catenin, an apoptotic target protein. Beevenom induced the Bax expressions, a pro-apoptotic gene, both in protein and mRNA levels, however, the levels of Bcl-$X_{S/L}$ expression, an anti-apoptotic gene, were down-regulated in Beevenom-treated cells. Western blot analysis and RT-PCT data revealed that the levels of cyclin of B1 protein and cyclin E mRNA were reduced by Beevenom treatment in MCF-7 cells, respectively, where as the expression of tumor suppressor p53 and cyclin dependent kinase inhibitor p21 mRNA were markedly increased in a concentration-dependent fashion. Conclusions : Taken together, these findings suggest that Beevenom induced inhibition of human breast cancer cell proliferation is associated with the induction of apoptotic cell death and Beevenom may have therapeutic potential in human breast cancer.

• Environmental Analysis Health and Toxicology
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• v.27
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• pp.10.1-10.7
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• 2012

Objectives: In recent years, a number of structurally diverse Histone deacetylase (HDAC) inhibitors have been identified and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. This study aimed at investigating the antitumor activity of newly synthesized HDAC inhibitor, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide (IN-2001) using human breast cancer cells. Methods: We have synthesized a new HDAC inhibitor, IN-2001, and cell proliferation inhibition assay with this chemical in estrogen receptor-positive human breast cancer MCF-7 cells. Cell cycle analysis on MCF-7 cells treated with IN-2001 was carried out by flow cytometry and gene expression was measured by RT-PCR. Results: In MCF-7 cells IN-2001 showed remarkable anti-proliferative effects in a dose- and time-dependent manner. In MCF-7 cells, IN-2001 showed a more potent growth inhibitory effect than that of suberoylanilide hydroxamic acid. These growth inhibitory effects were related to the cell cycle arrest and induction of apoptosis. IN-2001 showed accumulation of cells at $G_2$/M phase and of the sub-$G_1$ population in a time-dependent manner, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with HDAC inhibitor-mediated induction of CDK inhibitor expression. In MCF-7 cells, IN-2001 significantly increased $p21^{WAF1}$ expression. Conclusions: In summary, cyclin-dependent kinase (CDK) induced growth inhibition, possibly through modulation of cell cycle and apoptosis regulatory proteins, such as CDK inhibitors, and cyclins. Taken together, these results provide an insight into the utility of HDAC inhibitors as a novel chemotherapeutic regime for hormone-sensitive and insensitive breast cancer.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.113-113
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• 2001

Stable MCF-7-ERE cells, in which pERE-Luc reporter gene has been stably integrated into the genome of the MCF-7 cells, were used to detect the estrogenic activity of various dietary flavonoids in either pure chemical or mixtures. Estradiol (E2) induced luciferase activity in dose dependent manner and this activity was inhibited by tamoxifen (Tam) concomitant treatment. A large series of flavonoids showed estrogenic activities, corresponding to EC5O values between 0.2 and 9 microM and their mixtures didn't show additive or synergistic effects. And we could find some structure and activity relationship. First, 4-methoxylation and catechol structure decreased estrogenic activities. Second, hydroxylation of 3 position reduced estrogenic effect. Third glycosides of flavonoids showed weak estrogenic activity or no activity. Interestingly, when tested at high concentrations, genistein, kaempferol, biochanin A and chrysin elicited luciferase induction higher than that of the maximum induction by estradiol. And these effects of genistein and kaempferol could not be fully inhibited with tamoxifen

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2661-2665
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• 2016

Silibinin is a natural polyphenol with high antioxidant and anticancer properties. In this study, its influence on two of the most commonly employed human breast cancer cell lines, MCF-7 and T47D, and one non-malignant MCF-10A cell line, were investigated and compared. Cell viability, the cell cycle distribution and apoptosis induction were analyzed by MTT and flow cytometry, respectively. The effect of silibinin on PTEN, Bcl-2, P21, and P27 mRNAs expression was also investigated by real-time RT-PCR. It was found that silibinin caused G1 cell cycle arrest in MCF-7 and MCF-10A cells but had no effect on the T47D cell cycle. Silibinin induced cytotoxic and apoptotic effects in T47D cells more than the MCF-7 cells and had no cytotoxic effect in MCF-10A cells under the same conditions. Silibinin upregulated PTEN in MCF-7 and caused slightly increased P21 mRNA expression in T47D cells and slightly increased PTEN and P21 expression in MCF-10A cells. Bcl-2 expression decreased in all of the examined cells under silibinin treatment. P27 mRNA expression upregulated in T47D and MCF-10A cells under silibinin treatment. PTEN mRNA in T47D and P21 and P27 mRNAsin MCF-7 were not affected by silibinin. These results suggest that silibinin has mostly different inhibitory effects in breast cancer cells and might be an effective anticancer agent for some cells linked to influence on cell cycle progression.

• The Journal of Internal Korean Medicine
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• v.36 no.1
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• pp.13-21
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• 2015

Objectives : In Korea, Rhus verniciflua Stokes (RVS) has been used in traditional medicine for various diseases such as back pain, syndromes of the blood system in women, gastrointestinal disease, and cancer. However, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated yet. Methods : This study investigated the possible mechanisms by which RVS extract (RVE) exerts its anti-proliferative action in cultured human breast carcinoma MCF-7 cells. Results : Treatment with RVE in MCF-7 cells resulted in inhibition of cell viability through G1 arrest of the cell cycle and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by RVE treatment was associated with the inhibition of cyclin D1, cyclin-dependent kinase (Cdk) 2, retinoblastoma protein (pRB), and mouse double minute 2 (MDM2) expression. Moreover, RVE treatment concentration dependently increased the levels of tumor suppressor p53, which was associated with the marked induction of Cdk inhibitors such as p21 (Waf1/Cip1) and p27 (Kip1). However, the inhibition of p53 function by the wild-type p53-specific inhibitor, pifithrin-α, abolished the above-mentioned effects of RVE, showing that p53 was responsible for the cytotoxicity of RVE Conclusions : These data indicate that a molecular pathway involving p53-dependent G1 cell cycle arrest plays a pivotal role in the cellular response to RVE, and demonstrate the potential applications of RVE as an anti-cancer drug for breast cancer treatment.

• The Korean Journal of Food And Nutrition
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• v.21 no.4
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• pp.416-424
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• 2008

In an effort to elucidate the differential actions of blueberry(BB) in both normal and cancer cells, we utilized human breast cell lines to assess the accumulation of radical oxygen species(ROS) and ROS-associated apoptosis in both human normal breast epithelial(MCF10A) and breast cancer(MCF7) cells. BB extract was added to the cultures at a final concentration of $20{\mu}g/m{\ell}$ for 0(control), 6, 12, and 24 hr intervals. The MCF10A cells evidenced no marked ROS accumulation in the presence of BB, whereas the MCF7 cells evidenced clear ROS accumulation upon BB treatment from 12 hours forward. The number of dying or dead cells did not increase in the BB-treated MCF10A cell groups, whereas that number increased profoundly from 12 hr forward. Furthermore, the expression levels of certain stress-related, and pro- and antiapoptotic gene products evidenced differential responses to BB treatment between the MCF10A and MCF7 cell groups. These results indicate that the components of BB extract differentiate cancer cells by not preventing ROS accumulation within cells and by inducing ROS-associated cell death in cancer cells. However, no marked ROS accumulation or induction of cell death was noted in the normal breast epithelial cells. The fact that BB extract exerted a differential effect on cancer cells opens further directions of research regarding the specific components that exert the differential BB-mediated effects in the selective prevention of normal cells and therapy for cancer tissues in the physiological body.

• Environmental Mutagens and Carcinogens
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• v.20 no.1
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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.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.180-180
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• 2003

Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, is involved in the suppression of growth of several types of tumors such as liposarcoma, cancers of breast, prostate, and colon, possibly through induction of cell cycle arrest and/or apoptosis.(omitted)