• The Journal of Korean Medicine
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• v.29 no.5
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• pp.111-117
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• 2008

Objectives and methods : Previous mechanistic studies suggest the cyclooxygenase-2 (COX-2) inhibitors represent the good candidates against tumor progression. MeOH extract of the stem barks of Euonymus alatus induced the strong inhibition of COX-2. A phenolic compound responsible for the anti- COX-2 known to involve in tumor adhesion and invasion has been studied through the methanol extracts. The compound, rosmarinic acid (ROS-A) was an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid. ROS-A showed a strong inhibitory effect of COX-2 activity in a concentration-dependent manner. Then we have measured the IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production related the immune regulation, induction of inflammatory related genes. Results and Conclusions :Hep3B cells produce proinflammatory cytokines of IL-1${\beta}$, IL-6 and TNF-${\alpha}$ while ROS A inhibited the cytokines production. Since IL-1${\beta}$, IL-6 and TNF-${\alpha}$ need the transcription factors such as nuclear factor- ${\kappa}$B (NF-${\kappa}$B) and activated protein-1 (AP-1), we measured the transcription factors. ROS-A inhibited the activation of p65, p50, c-Rel subunits of NF-${\kappa}$B and AP-1 transcription factors. These findings indicate that ROS A from the stem bark of E. alatus inhibits proliferation in metastatic cancer cells. It was suggested that stem barks of E. alatus could be suitable for anti-cancer drugs.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.651-656
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• 2006

This study examined the chemopreventive effect of saponins that were isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), against the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), -on lung tumorigenesis in A/J mice. The mice were treated with a single NNK dose (100 mg/kg b.w., i.p.). CKS (0.5, 1, 4 mg/kg body wt.) was administered orally daily for 3 days/week beginning 1 day after the NNK treatment and was maintained throughout the experiment. The administration of CKS suppressed the NNK-induced increase in the level of proliferating cell nuclear antigen, which are a marker of cell proliferation, in the lungs of the mice 4 weeks after the NNK injection. Twenty-five weeks after the NNK treatment, the mice were sacrificed and the number of surface lung tumors was measured. CKS significantly reduced the number of lung tumors induced by NNK in a dose dependent manner. These results suggest that CKS suppresses the development of lung tumors and has a chemopreventive effect against NNK-induced mouse lung tumorigenesis.

• Food Science and Biotechnology
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• v.18 no.3
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• pp.689-693
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• 2009

Germination is well-known to enhance the digestibility, functionality, and palatability of plant seeds. To examine the functionality of germinated-safflower seed (GSS), proliferative and differentiative effects of GSS extract on the mouse calvarial bone cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolinbromide (MTT) assay and alkaline phosphatase activity, respectively. Water extract of GSS increased dose-dependently proliferative and differentiative effects on calvarial bone cell, and its effects were stronger than those of ungerminated-safflower seeds (UGSS) extract. One major component was isolated from GSS extract by a series of purification procedure of solvent fractionation, Diaion HP-20, and Sephadex LH-20 column chromatographies. Its chemical structure was identified as trachelogenin (TC) by nuclear magnetic resonance (NMR) and mass spectrometry (MS) spectral analysis. Trachelogenin showed significant proliferative (125.7%) and differentiative (132.1%) effects on calvarial bone cells at $10^{-8}M$, and its effects were significantly higher than those of $17{\beta}-estradiol\;(E_2)$. TC was found to be a major active compound responsible for high proliferative and differentative effects of the water extract of GSS. Therefore, these results suggest that TC in GSS may be useful as potential therapeutic agent for the prevention and treatment of bone loss.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.327-334
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• 2015

The cytoprotective enzyme heme oxygenase-1 (HO-1) influences endothelial cell survival, proliferation, inflammatory response, and angiogenesis in response to various angiogenic stimuli. In this study, we investigate the involvement of HO-1 in the angiogenic activity of orexin-A. We showed that orexin-A stimulates expression and activity of HO-1 in human umbilical vein endothelial cells (HUVECs). Furthermore, we showed that inhibition of HO-1 by tin (Sn) protoporphryin-IX (SnPP) reduced orexin- A-induced angiogenesis in vivo and ex vivo. Orexin-A-stimulated endothelial tube formation and chemotactic activity were also blocked in SnPP-treated vascular endothelial cells. Orexin-A treatment increased the expression of nuclear factor erythroid-derived 2 related factor 2 (Nrf2), and antioxidant response element (ARE) luciferase activity, leading to induction of HO-1. Collectively, these findings indicate that HO-1 plays a role as an important mediator of orexin-A-induced angiogenesis, and provide new possibilities for therapeutic approaches in pathophysiological conditions associated with angiogenesis.

• Journal of the Korean Magnetic Resonance Society
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• v.23 no.1
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• pp.12-19
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• 2019

A former study has shown that the spin-lattice relaxation time ($T_1$) in cancerous prostate tissue had enhanced contrast at an ultra-low magnetic field, $132{\mu}T$. To study the field dependence and the origin of the contrast we measured $T_1$ in pairs of ex-vivo prostate tissues at the Earth's magnetic field. A portable and coil-based nuclear magnetic resonance (NMR) system was adopted for $T_1$ measurements at $40{\mu}T$. The $T_1$ contrast, ${\delta}=1-T_1$ (more cancer)/$T_1$(less cancer), was calculated from each pair. Additionally, we performed pathological examinations such as Gleason's score, cell proliferation index, and micro-vessel density (MVD), to quantify correlations between the pathological parameters and $T_1$ of the cancerous prostate tissues.

• Fisheries and Aquatic Sciences
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• v.24 no.1
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• pp.1-9
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• 2021

Human prostate cancer is the second most frequently diagnosed cancer worldwide, and its incidence rate continues to increase. Advanced prostate cancer is more difficult to treat than early forms due to its chemotherapy resistance. There is need for more effective agents that can inhibit the progression of advanced prostate cancer. Demethoxyfumitremorgin C (DMFTC) was isolated from the fermentation extract of the marine fungus Aspergillus fumigatus. Antiproliferative activity of DMFTC against human prostate cancer PC3 cells was examined through cell cycle analysis by flow cytometry, the fluorescent nuclear imaging analysis with propidium iodide (PI), and proteins expression related to cell cycle arrest and apoptosis were investigated via Western blotting. DMFTC inhibited PC3 cells growth through G1 phase cell cycle arrest and apoptosis induction. It activated the tumor suppressor p53 and the Cdk inhibitor p21, which regulate the cell progression into the G1 phase. Additionally, PI-positive late apoptotic non-viable cells were increased and the expression levels of the G1-positive downstream regulators cyclin D, cyclin E, Cdk2, and Cdk4 were decreased by DMFTC treatment. These results suggest that DMFTC induces G1 arrest and apoptosis induction through regulation of p53/p21-dependent cyclin-Cdk complexes, and it may be a useful therapeutic agent for the treatment of human advanced prostate cancer.

• International Journal of Oral Biology
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• v.45 no.4
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• pp.152-161
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• 2020

D-pinitol is an analog of 3-methoxy-D-chiro-inositol found in beans and plants. D-pinitol has anti-inflammatory, antidiabetic, and anticancer effects. Additionally, D-pinitol induces apoptosis and inhibits metastasis in breast and prostate cancers. However, to date, no study has investigated the anticancer effects of D-pinitol in oral cancer. Therefore, in this study, whether the anticancer effects of D-pinitol induce apoptosis, inhibit the epithelial-to-mesenchymal transition (EMT), and arrest cell cycle was investigated in squamous epithelial cells. D-pinitol decreased the survival and cell proliferation rates of CAL-27 and Ca9-22 oral squamous carcinoma cells in a concentration- and time-dependent manner. Evidence of apoptosis, including nuclear condensation, poly (ADP-ribose) polymerase, and caspase-3 fragmentation, was also observed. D-pinitol inhibited the migration and invasion of both cell lines. In terms of EMT-related proteins, E-cadherin was increased, whereas N-cadherin, Snail, and Slug were decreased. D-pinitol also decreased the expression of cyclin D1, a protein involved in the cell cycle, but increased the expression of p21, a cyclin-dependent kinase inhibitor. Hence, D-pinitol induces apoptosis and cell cycle arrest in CAL-27 and Ca9-22 cells, demonstrating an anticancer effect by decreasing the EMT.

• Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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• v.19 no.4
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• pp.447-457
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• 2021

Graphite Isotope Ratio Method (GIRM) can be used to estimate plutonium production in a graphite-moderated reactor. This study presents verification results for the GIRM combined with a 3-D polynomial regression function to estimate cumulative plutonium production in a graphite-moderated reactor. Using the 3-D Monte-Carlo method, verification was done by comparing the cumulative plutonium production with the GIRM. The GIRM can estimate plutonium production for specific sampling points using a function that is based on an isotope ratio of impurity elements. In this study, the ¹⁰B/¹¹B isotope ratio was chosen and calculated for sampling points. Then, 3-D polynomial regression was used to derive a function that represents a whole core cumulative plutonium production map. To verify the accuracy of the GIRM with polynomial regression, the reference value of plutonium production was calculated using a Monte-Carlo code, MCS, up to 4250 days of depletion. Moreover, the amount of plutonium produced in certain axial layers and fuel pins at 1250, 2250, and 3250 days of depletion was obtained and used for additional verification. As a result, the difference in the total cumulative plutonium production based on the MCS and GIRM results was found below 3.1% with regard to the root mean square (RMS) error.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10407-10412
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• 2015

Background: ${\beta}$-elemene, extracted from herb medicine Curcuma wenyujin has potent anti-tumor effects in various cancer cell lines. However, the activity of ${\beta}$-elemene against glioma cells remains unclear. In the present study, we assessed effects of ${\beta}$-elemene on human glioma cells and explored the underlying mechanism. Materials and Methods: Human glioma U87 cells were used. Cell proliferation was determined with MTT assay and colony formation assay to detect the effect of ${\beta}$-elemene at different doses and times. Fluorescence microscopy was used to observe cell apoptosis with Hoechst 33258 staining and change of glioma apoptosis and cell cycling were analyzed by flow cytometry. Real-time quantitative PCR and Western-blotting assay were performed to investigated the influence of ${\beta}$-elemene on expression levels of Fas/FasL, caspase-3, Bcl-2 and Bax. The experiment was divided into two groups: the blank control group and ${\beta}$-elemne treatment group. Results: With increase in the concentration of ${\beta}$-elemene, cytotoxic effects were enhanced in the glioma cell line and the concentration of inhibited cell viability ($IC_{50}$) was $48.5{\mu}g/mL$ for 24h. ${\beta}$-elemene could induce cell cycle arrest in the G0/G1 phase. With Hoechst 33258 staining, apoptotic nuclear morphological changes were observed. Activation of caspase-3,-8 and -9 was increased and the pro-apoptotic factors Fas/FasL and Bax were upregulated, while the anti-apoptotic Bcl-2 was downregulated after treatment with ${\beta}$-elemene at both mRNA and protein levels. Furthermore, proliferation and colony formation by U87 cells were inhibited by ${\beta}$-elemene in a time and does-dependent manner. Conclusions: Our results indicate that ${\beta}$-elemene inhibits growth and induces apoptosis of human glioma cells in vitro. The induction of apoptosis appears to be related with the upregulation of Fas/FasL and Bax, activation of caspase-3,-8 and -9 and downregulation of Bcl-2, which then trigger major apoptotic cascades.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.437-442
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• 2015

Aim: To establish a pancreatic cancer stem cell model using human pancreatic cancer cells in nude mice to provide a platform for pancreatic cancer stem cell research. Materials and Methods: To establish pancreatic cancer xenografts using human pancreatic cancer cell line SW1990, nude mice were randomly divided into control and gemcitabine groups. When the tumor grew to a volume of $125mm^3$, they treated with gemcitabine at a dose of 50mg/kg by intraperitoneal injection of 0.2ml in the gemcitabine group, while the mice in control group were treated with the same volume of normal saline. Gemcitabine was given 2 times a week for 3 times. When the model was established, the proliferation of pancreatic cancer stem cells was observed by clone formation assay, and the protein and/or mRNA expression of pancreatic stem cell surface markers including CD24, CD44, CD133, ALDH, transcription factors containing Oct-4, Sox-2, Nanog and Gli, the key nuclear transcription factor in Sonic Hedgehog signaling pathway was detected by Western blot and/or RT-PCR to verify the reliability of this model. Results: This model is feasible and safe. During the establishment, no mice died and the weight of nude mice maintained above 16.5g. The clone forming ability in gemcitabine group was stronger than that of the control group (p<0.01). In gemcitabine group, the protein expression of pancreatic cancer stem cell surface markers including CD44, and ALDH was up-regulated, the protein and mRNA expression of nuclear transcription factor including Oct-4, Sox-2 and Nanog was also significantly increased (P<0.01). In addition, the protein expression of key nuclear transcription factor in Sonic Hedgehog signaling pathway, Gli-1, was significantly enhanced (p<0.01). Conclusions: The pancreatic cancer stem cell model was successfully established using human pancreatic cancer cell line SW1990 in nude mice. Gemcitabine could enrich pancreatic cancer stem cells, simultaneously accompanied by the activation of Sonic Hedgehog signaling pathway.