• Journal of the Korean Chemical Society
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• v.55 no.6
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• pp.952-959
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• 2011

Novel phosphorylated derivatives of ribavirin 5-16 were synthesized by the reaction of 4-nitrophenyl phosphorodichloridate with various amino acid esters in the presence of triethylamine in dry tetrahydrofuran through the intermediates 3. On further reaction of 3 with ribavirin in THF and pyridine in the presence of TEA afforded the title compounds 5-16. Their structures were characterized by IR, $^1H$, $^{13}C$, $^{31}P$ NMR and mass spectral analyses. All the title compounds were found to exhibit potent in vitro anticancer activity against MCF-7 breast cancer cell lines.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8617-8622
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• 2014

The goal of this study was to establish paclitaxel resistant MCF-7 cells, as in vitro model, to identify the molecular mechanisms leading to acquired chemoresistance in breast cancer cells. Resistant cells were developed by stepwise increasing exposure to paclitaxel. Gene expression levels of Bax and Bcl-2 along with protein levels of caspase-8 and caspase-9 were evaluated in two resistant cell lines (MCF-7/Pac64 and MCF-7/Pac5 nM). Morphological modifications in paclitaxel resistance cells were examined by light microscopy and fluorescence activated cell sorting (FACS). As an important indicator of resistance to chemotheraputic agents, the Bcl-2/Bax ratio showed a significant increase in both MCF-7/Pac5nM and MCF-7/Pac 64nM cells (p<0.001), while caspase-9 levels were decreased (p<0.001) and caspase-8 was increased (p<0.001). FACS analysis demonstrated that MCF-7/Pac64 cells were smaller than MCF-7 cells with no difference in their granularity. Our results support the idea that paclitaxel induces apoptosis in a mitochondrial-dependent manner. Identifying breast cancer patients with a higher Bcl-2/Bax ratio and caspase 9 level and then inhibiting the activity of these proteins may improve the efficacy of chemotheraputic agents.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.139-139
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• 1998

Effects of TCDD and flavonoids on ethoxyresorufin deethylase in Hepa I cells and MCF-7 human breast cancer cells were examined. TCDD treatment have resulted in the stimulation of ethoxyresorufin deethylase activity based on fluorometry in Hepa I in dose and time dependent manner. 0.1 nM TCDD showed maximal stimulation of ethoxyresorufin deethylase activity and 24 hour treatment also showed maximal stimulation of ethoxyresorufin deethylase activity. In MCF-7 human breast cancer cells, untreated cells showed high basal level of ethoxyresorufin deethylase activity. TCDD treatment to MCF-7 cells resulted minor stimulation of ethoxyresorufin deethylase activity compared to that in Hepa I cells. Various chemicals were tested for ethoxyresorufin deethylase activity in both cell lines. Flavonoids, such as quercetin showed an inhibition of ethoxyresorufin deethylase activity that is stimulated with TCDD or 3-Methylcholanthrene. Estrogen and estrogen metabolites such as 16a-estriol also affects the ethoxyresorufin deethylase activity in MCF-7 cells.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.138-138
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• 1998

Effects of nitric oxide and hypoxia on ethoxyresorufin deethylase in Hepa I cells and MCF-7 human breast cancer cells were examined. TCDD treatment have resulted in the stimulation of ethoxyresorufin deethylase activity based on fluorometry in Hepa I in dose and time dependent manner. 0.1 nM TCDD showed maximal stimulation of ethoxyresorufin deethylase activity and 24 hour treatment also showed maximal stimulation of ethoxyresorufin deethylase activity. In MCF-7 human breast cancer cells, untreated cells showed high basal level of ethoxyresorufin deethylase activity. TCDD treatment to MCF-7 cells resulted minor stimulation of ethoxyresorufin deethylase activity compared to that in Hepa I cells. Nitric oxide and hypoxia inhibit TCDD effects on ethoxyresorufin deethylase activity in both cell lines. And also flavonoids, such as quercetin showed an inhibition of ethoxyresorufin deethylase activity that is stimulated with TCDD or 3-Methylcholanthrene. Estrogen and estrogen metabolite such as 16 a-estriol and 2-hydroxyestradiol also affects the ethoxyresorufin deethylase activity in MCF-7 cells.

• Journal of Nutrition and Health
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• v.40 no.2
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• pp.147-153
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• 2007

In this study, we investigated the anticancer activity of the fin of Thunnus Thynnus (TT). TT was extracted with methanol (TTM), and then further fractionated into four subfractions by using solvent partition method, affording hexane (TTMH), methanol (TTMM), butanol (TTMB) and aquous (TTMA) soluble fractions. We determined the cytotoxicity of these four fractions in four kind of cancer cell lines, such as HepG2, MCF-7, B16-F10 and HT29 by MTT assay. The TTMM showed the strongest cytotoxic effect at the concentration of 150 ${\mu}g/mL$, displaying 95% on the HepG2 cell lines and 82% on MCF-7 cell line. The morphological changes such as membrane shirinking and blebbing of cells were also observed by TTMM treatment in HT29 cell. In addition, we observed that quinone reductase (QR) activity was elevated by only TTMM and TTMH treatments in HepG2 cell. QR activity was increased to around 2.0 and 1.8 times in TTMM and TTMH treated HepG2 cell at 100 ${\mu}g/mL$, respectively, compared to that in control. Although further studies are needed, the present work could suggest that the fin of TT has a potential to be usable as a chemopreventive agent against cancer.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.136-136
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• 2002

Experiments were carried out to determine the role of Raf-1 kinase in the development of drug resistance and apoptosis induced by paclitaxel. In the present study, paclitaxel sensitivity, Raf-1 activity and MAPKs activation were compared in 2 cell lines: parental human breast cancer cells and its drug resistant variant (MCF-7/Adr) cells.(omitted)

• 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)

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5865-5869
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• 2012

RHOXF1 has been shown to be expressed in embryonic stem cells, adult germline stem cells and some cancer lines. It has been proposed as a candidate gene to encode transcription factors regulating downstream genes in the human testis with antiapoptotic effects. Its expression in cancer cell lines has implied a similar role in the process of tumorigenesis. The human breast cancer cell lines MDA-MB-231 and MCF-7 were cultured in DMEM medium and transfected with a pGFP-V-RS plasmid bearing an RHOXF1 specific shRNA. Quantitative real-time RT-PCR was performed for RHOXF1, CASP8, BCL2 and HPRT genes. Decreased RHOXF1 expression was confirmed in cells after transfection. shRNA knock down of RHOXF1 resulted in significantly decreased BCL2 expression in both cell lines but no change in CASP8 expression. shRNA targeting RHOXF1 was shown to specifically mediate RHOXF1 gene silencing, so RHOXF1 can mediate transcriptional activation of the BCL2 in cancers and may render tumor cells resistant to apoptotic cell death induced by anticancer therapy. shRNA mediated knock down of RHOXF1 can be effective in induction of apoptotic pathway in cancer cells via BCL2 downregulation, so it can have potential therapeutic utility for human breast cancer.

• Archives of Pharmacal Research
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• v.26 no.8
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• pp.620-630
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• 2003

The proliferative effects of thirty Oriental medicinal herbs on MCF-7 (estrogen-sensitive breast cancer cell line) and ROS 17/2.8 osteoblast-like cells were determined using the MTT assay. Methanol extracts from several herbs was found to show proliferative activity on the above two cell lines in the range of 5 to 100 $\mu$g/mL. Among these active herbs, the methanol extract from the rhizomes of Drynaria fortunei showed the most potent proliferative activity, and the cell proliferations were significantly increase by 136 and 158% in the MCF-7 and ROS 17/2.8 cells, respectively, when treated with 100 $\mu$ g/mL. Through a bioassay-guided separation, eight flavonoids, including four new flavan-3-ols and two propelargonidins, together with the known (-)-epiafzelechin and naringin, were isolated. Their chemical structures were characterized as (-)-epiafzelechin (1), (-)-epiafzelechin-3-O-$\beta$-D-allopyranoside (2), (-)-epiafzelechin-3-O-(6"-O-acetyl)-$\beta$-D-allopyranoside (3), 4$\beta$-carboxymethyl-(-)-epiafzelechin methyl ester (4), 4$\beta$-car-boxymethyl-(-)-epiafzelechin sodium salt (5), naringin (6), (-)-epiafzelechin-(4$\beta$\rightarrow8)-4$\beta$-car-boxymethylepiafzelechin methyl ester (7) and (-)-epiafzelechin-($4\beta\rightarrow8, 2\beta\rightarrowΟ\rightarrow7)-epiafzelechin-(4\beta\righarrow8)-epiafzelechin (8) by extensive 1D and 2D NMR spectroscopy. Most of these flavonoids, in the range of $10^{-15}∼10^{-6}$ M, accelerated the proliferation of MCF-7 cell, with compounds 7 and 8, in the range of $10^{-15}∼10^{-12}$ M, showing especially potent proliferation effects. Meanwhile, seven flavonoids, with the exception of compound 4, stimulated the proliferation of ROS 17/2.8 cells in the range of $10^{-15}∼10^{-6}$ M, with compounds 5-8 especially accelerating the proliferation, in dose-dependent manners ($10^{-15}∼10^{-9}$ M), and their proliferative effect was much stronger than that of $E_2$ and genistein. These results suggest that propelargonidin dimers and trimers isolated from the rhizomes of Drynaria fortunei may be useful as potential phytoestrogens, which play important physiological roles in the prevention of postmenopausal osteoporosis.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.384-389
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• 2014

Adiponectin, an adipokine predominantly secreted from adipose tissue, exhibits diverse biological responses, including metabolism of glucose and lipid, and apoptosis in cancer cells. Recently, adiponectin has been shown to modulate autophagy as well. While emerging evidence has demonstrated that autophagy plays a role in the modulation of proliferation and apoptosis of cancer cells, the role of autophagy in apoptosis of cancer cell caused by adiponectin has not been explored. In the present study, we demonstrated that globular adiponectin (gAcrp) induces both apoptosis and autophagy in human hepatoma cell line (HepG2 cells) and breast cancer cells (MCF-7), as evidenced by increase in caspase-3 activity, Bax, microtubule-associated protein light chain 3-II (LC3 II) protein levels, and autophagosome formation. Interestingly, gene silencing of LC3B, an autophagy marker, significantly enhanced gAcrp-induced apoptosis in both HepG2 and MCF-7 cell lines, whereas induction of autophagy by rapamycin, an mTOR inhibitor, significantly prevented gAcrp-induced apoptosis in hepatoma cells HepG2. Furthermore, modulation of autophagy produced similar effects on gAcrp-induced Bax expression in HepG2 cells. These results implicate that induction of autophagy plays a regulatory role in adiponectin-induced apoptosis of cancer cells, and thus inhibition of autophagy would be a novel promising target to enhance the efficiency of cancer cell apoptosis by adiponectin.