• Archives of Pharmacal Research
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• v.20 no.6
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• pp.579-585
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• 1997

To gain further insight into the mechanism of action of antiestrogens, we examined the interaction of antiestrogen with the estrogen receptor system and with estrogen- noncompetable antiestrogen binding sites. In addition to binding directly to the estrogen receptor, antiestrogens can be found associated with binding sites that are distinct from the estrogen receptor. In contrast to the restriction of estrogen receptors to estrogen target cells, such as those of uterus and mammary glands, antiestrogen binding sites are present in equal amounts in estrogen receptor-positive and -negative human breast cancer cell lines, such as MCF-7, T47D, and MDA-MB-231 that differ markedly in their sensitivity to antiestrogens. In order to gain greater insight into the role of these antiestrogen binding sites in the action of antiestrogens, we have examined the biopotency of different antiestrogens for the antiestrogen binding sites and that is CI628 > tamoxifen > trans-hydroxy tamoxifen > CI628M > H1285 > LY117018. This order of affinities does not parallel the affinity of these compounds for the estrogen receptor nor the potency of these compounds as antiestrogens. Indeed, compounds with high affinity for the estrogen receptor and greatest antiestrogenic potency have low affinities for these antiestrogen binding sites. Antiestrogenic potency correlates best with estrogen receptor affinity and not with affinity for antiestrogen binding sites. In summary, our findings suggested that interaction with the estrogen receptor is most likely the mechanism through which antiestrogens evoke their growth inhibitory effects.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.291-297
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• 2013

Notch1 has been reported to be highly expressed in triple-negative and other subtypes of breast cancer. Mutant p53 (R280K) is overexpressed in MDA-MB-231 triple-negative human breast cancer cells. The present study aimed to determine whether the mutant p53 can be a potent transcriptional activator of the Notch1 in MDA-MB-231 cells, and explore the role of this mutant p53-Notch1 axis in curcumin-induced apoptosis. We found that curcumin treatment resulted in an induction of apoptosis in MDA-MB-231 cells, together with downregulation of Notch1 and its downstream target, Hes1. This reduction in Notch1 expression was determined to be due to the decreased activity of endogenous mutant p53. We confirmed the suppressive effect of curcumin on Notch1 transcription by performing a Notch1 promoter-driven reporter assay and identified a putative p53-binding site in the Notch1 promoter by EMSA and chromatin immunoprecipitation analysis. Overexpression of mutant p53 increased Notch1 promoter activity, whereas knockdown of mutant p53 by small interfering RNA suppressed Notch1 expression, leading to the induction of cellular apoptosis. Moreover, curcumin-induced apoptosis was further enhanced by the knockdown of Notch1 or mutant p53, but it was decreased by the overexpression of active Notch1. Taken together, our results demonstrate, for the first time, that Notch1 is a transcriptional target of mutant p53 in breast cancer cells and suggest that the targeting of mutant p53 and/or Notch1 may be combined with a chemotherapeutic strategy to improve the response of breast cancer cells to curcumin.

• Journal of Microbiology and Biotechnology
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• v.16 no.9
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• pp.1405-1409
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• 2006

Polysaccharides from the starfish Asterina pectinifera were assessed in vitro for their chemopreventive potential in human breast cancer. The polysaccharides from A. pectinifera inhibited cell proliferation in the estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. In addition, the polysaccharides were found to be an inhibitor of cytochrome P450 1A1-mediated ethoxyresorufin O-deethylase activity, and caused a dose-dependent inhibition of aromatase activity in microsomes isolated from a human placenta. There was a significant reduction in the ornithine decarboxylase activity to 30.7% of the control in the polysaccharide-treated MCF-7 breast cancer cells. Therefore, the polysaccharides from A. pectinifera merit further investigation with respect to breast cancer chemoprevention.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.404-410
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• 2017

Benzylideneacetophenone derivative (1E)-1-(4-hydroxy-3-methoxyphenyl) hept-1-en-3-one (JC3) elicited cytotoxic effects on MDA-MB 231 human breast cancer cells-radiation resistant cells (MDA-MB 231-RR), in a dose-dependent manner, with an $IC_{50}$ value of $6{\mu}M$ JC3. JC3-mediated apoptosis was confirmed by increase in sub-G1 cell population. JC3 disrupted the mitochondrial membrane potential, and reduced expression of anti-apoptotic B cell lymphoma-2 protein, whereas it increased expression of pro-apoptotic Bcl-2-associated X protein, leading to the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase. In addition, JC3 activated mitogen-activated protein kinases, and specific inhibitors of these kinases abrogated the JC3-induced increase in apoptotic bodies. JC3 increased the level of intracellular reactive oxygen species and enhanced oxidative macromolecular damage via lipid peroxidation, protein carbonylation, and DNA strand breakage. Considering these findings, JC3 is an effective therapy against radiation-resistant human breast cancer cells.

• Journal of Life Science
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• v.19 no.11
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• pp.1581-1590
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• 2009

Hizikia fusiforme is a kind of brown edible seaweed that mainly grows in the temperate seaside areas of the northwest pacific, including Korea, Japan and China, and has been widely used as a health food for hundreds of years. Recently, H. fusiforme has been known to exert pharmacological activities including antioxidant, antimutagenic and anticoagulant activities. However, the molecular mechanisms of H. fusiforme in malignant cells have not been clearly elucidated yet. In this study, the effects of ethyl alcohol extract of H. fusiforme (EAHF) on the anti-proliferative effects of MDA-MB-231 and MCF-7 human breast cancer cells were investigated. EAHF treatment resulted in a concentration-dependent growth inhibition by including apoptosis in MDA-MB-231 cells and G1 phase arrest in MCF-7 cells, which could be proved by MTT assay, DAPI staining, agarose gel electrophoresis and flow cytometry analysis. In MDA-MB-231 cells, the increase in apoptosis induced by EAHF treatment correlated with up-regulation of pro-apoptotic Bax expression. EAHF treatment induced the proteolytic activation of caspase-3 and caspase-9, and a concomitant inhibition of poly (ADP-ribose) polymerase, $\beta$-catenin, phospholipase-${\gamma}1$ protein and DNA fragmentation factor 45/inhibitor of caspase-activated DNase. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. fusiforme.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.2
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• pp.71-75
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• 2006

The effect of protein extract from Asterina pectinifera on proliferation of human breast cancer cells and activities of cytochrome P450 1A1 and ornithine decarboxylase was tested. Protein extract from Asterina pectinifera inhibited the growth of both estrogen-dependent MCF-7 and estrogen-independent MDA-MB-231 human breast cancer cells. Cytochrome P450 1A1 activity was significantly inhibited by the protein extract from Asterina pectinifera at concentrations of 80 (p<0.05), 120 (p<0.01) and $160{\mu}g/m{\ell}$ (p<0.01). The extract inhibited induction of ornithine decarboxylase by 12-O-tetradecanoylphorbol-13-acetate, a key enzyme of polyamine biosynthesis, which is enhanced in breast tumor promotion. Therefore, Asterina pectinifera is worth further investigation with respect to breast cancer chemoprevention or therapy.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.62-66
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• 2016

Amygdalin, D-mandelonitrile-${\beta}$-D-glucoside-6-${\beta}$-glucoside, belongs to aromatic cyanogenic glycoside group derived from rosaceous plant seed. Mounting evidence has supported the anti-cancer effects of amygdalin. However, whether amygdalin indeed acts as an anti-tumor agent against breast cancer cells is not clear. The present study aimed to investigate the effect of amygdalin on the proliferation of human breast cancer cells. Here, we show that amygdalin exerted cytotoxic activities on estrogen receptors (ER)-positive MCF7 cells, and MDA-MB-231 and Hs578T triple-negative breast cancer (TNBC) cells. Amygdalin induced apoptosis of Hs578T TNBC cells. Amygdalin downregulated B-cell lymphoma 2 (Bcl-2), upregulated Bcl-2-associated X protein (Bax), activated of caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Amygdalin activated a pro-apoptotic signaling molecule p38 mitogen-activated protein kinases (p38 MAPK) in Hs578T cells. Treatment of amygdalin significantly inhibited the adhesion of Hs578T cells, in which integrin ${\alpha}5$ may be involved. Taken together, this study demonstrates that amygdalin induces apoptosis and inhibits adhesion of breast cancer cells. The results suggest a potential application of amygdalin as a chemopreventive agent to prevent or alleviate progression of breast cancer, especially TNBC.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.107-107
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• 1997

Cytochrome P450 enzymes have been intensively investigated in hepatic tissues and several mammalian cell lines. Compared to most studies about cytochrome P450 isozymes in liver in vivo and hepatic, cell lines in vitro, the study of cytochrome P450IA1 in human breast cancer cells could be very important to understand the mechanism of the regulation of CYPIA1 gene expression and cell growth. MCF-7 human breast cancer cells are well characterized to study estrogen and antiestrogen action due to the fact that they contain high level of estrogen receptor and have biological markers characterized. And also MCF-7 cells express high level of arylhydrocarbon hydroxylase activity and human cytochrome P450IA1 cDNA was cloned from MCF-7 cells. Ah receptor was characterized in many breast cancer cell lines and polycyclic aromatic hydrocarbon such as 3-MC induced the expression of CYPIA1 gene and cytochrome P450- dependent monooxygenase activity. We undertook a study to examine the effect of estrogens and other chemicals on the regulation of human CYPIA1 gene expression in MCF-7 cells via RTPCR analysis, that might help us to understand the mechanism of the regulation of CYPIA1 gene expression and MCF-7 cell growth. Expression vector containing the functional 5'-regulatory region of human CYPIA1 fused to the CAT reporter gene was transfected into estrogen receptor positive MCF-T cells or estrogen receptor negative MDA-MB-231 cells. After these cells were treated with various chemicals, RTPCR was carried out to measure both CYPIA1 mRNA and CAT mRNA levels. 1nM 3-MC increased in both P450 and CAT mRNA levels over those of control by two folds in MCF-7 cells but does not in MDA-MB-231 cells. Estrogen or tamoxifen or retinoic acid or chrysin decreased in both P450 and CAT mRNA levels that were induced by 3-MC in MCF-7 when each chemical was administered with 3-MC concomitantly. These results suggested that the level of CYPIA1 gene expression is modulated with estrogen-related molecules and make it possible to speculate that ER is related to CYPIA1 gene expression and cell growth in breast cancer cells. [Supported by grants from the Korean Ministry of Education ]

• Natural Product Sciences
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• v.25 no.1
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• pp.72-75
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• 2019

Bioassay-guided fractionation of the roots of Asarum sieboldii led to the isolation of the six compounds methylkakuol (1), sesamin (2), asarinin (3), xanthoxylol (4), and (2E,4E,8Z,10E/Z)-N-(2-methylpropyl) dodeca-2,4,8,10-tetraenamide (5/6). Among the isolates, xanthoxylol (4) exhibited significant cytotoxicity against human breast cancer cells MCF-7 and MDA-MB-231 in vitro with $IC_{50}$ values of 9.15 and $13.95{\mu}M$, respectively.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.115.1-115.1
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• 2003

Cadmium, a human carcinogen, can induce apoptosis in various cell lines. Despite extensive research, the mechanisms of cadmium-induced apoptosis are poorly understood, and its toxicity and estrogenic potential in human are not clear. This study was performed to investigate the apoptotic activities of cadmium on two human breast cancer cell lines: MCF-7 cells, an estrogen receptor (ER) positive cell line, and MDA-MB-231 cells, an ER negative cell line. Both cells were treated with $CdCl_2$ 100$\mu$M for 12hrs, and the spoptosis was determined by DNA fragmentation, DAPI staining, and expression of caspase-9. (omitted)