• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5805-5810
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• 2013

This study was conducted to analyze the molecular mechanisms responsible for anti-proliferation effects of glaucocalyxin A in cultured MCF-7 and Hs578T breast cancer cells. The concentration that reduced cell viability to 50% (IC50) after 72 h treatment was derived and potential molecular mechanisms of anti-proliferation using the IC50 were investigated as changes in cell cycle arrest and apoptosis. Gene and protein expression changes related to apoptosis were investigated by semi-quantitative RT-PCR and western blotting, respectively. Involvement of phosphorylated mitogen-activated protein kinases and JNK signaling in regulation of these molecules was characterized by western blotting. Cell viability decreased in a concentration-dependent manner and the IC50 was determined as $1{\mu}M$ in MCF-7 and $4{\mu}M$ in Hs578T cell. Subsequently, we demonstrated that the GLA-induced MCF-7 and Hst578T cell death was due to cell cycle arrest at the G2/M transition and was associated with activation of the c-jun N-terminal kinase (JNK) pathway. We conclude that GLA has the potential to inhibit the proliferation of human breast cancer cells through the JNK pathway and suggest its application forthe effective therapy for patients with breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7641-7651
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• 2015

It has been shown previously that nutritional supplements rich in polyphenolic compounds play a significant role in prostate cancer chemoprevention. Propolis is a natural, resinous hive product that has several pharmacological activities including antimicrobial, antioxidant, anti-inflammatory, and antitumoral activities. The aim of this study was to compare the cytotoxic, antioxidant and antitumoral activities of an ethanolic extract of Egyptian propolis (EEP) in vitro with an established chemotherapeutic drug such as doxorubicin (DOX), and the effects of their combination against the PC3 human prostate cancer cell line. Cellular viability and $IC_{50}$ levels with EEP, DOX and their (v/v) combination were detected by sulphorhodamine-B (SRB) assay after incubation of PC3 cells for 72h with different doses (0, 0.01, 0.1, 1, 10 and $100{\mu}g/ml$). Two selected doses of $IC_{50}$ and $IC_{25}$ were applied to cells for 24h for antitumor evaluation assay of treatment compounds. EEP and its (v/v) combination with DOX showed significant antitumor potential besides high antioxidant properties of superoxide dismutase (SOD), total antioxidant capacity (TAC), catalase (CAT), nitric oxide (NO) and reduced glutathione (GSH) levels when compared with the control untreated cells. DNA fragmentation assay and semi quantitative RT-PCR analyses for p53 and Bax genes showed that EEP activated cellular apoptosis and increased the mRNA expression levels more than other treatment. In conclusion, EEP alone or in combination with DOX at both doses used here showed greater antioxidant, antiproliferative and apoptotic effects against the PC3 cell lines as compared to treatment with DOX alone. Therefore, EEP could be considered as a promising candidate for prostate cancer chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6945-6948
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• 2013

Background: Diosgenin, a steroidal saponin from a therapeutic herb, fenugreek (Trigonellafoenum-graceum L.), has been recognized to have anticancer properties. Telomerase activity is not detected in typical healthy cells, while in cancer cell telomerase expression is reactivated, therefore providing a promising cancer therapeutic target. Materials and Methods: We studied the inhibitory effect of diosgenin on human telomerase reverse transcriptase gene (hTERT) expression which is critical for telomerase activity. MTT- assays and qRT-PCR analysis were conducted to assess cytotoxicity and hTERT gene expression inhibition effects, respectively. Results: MTT results showed that $IC_{50}$ values for 24, 48 and 72h after treatment were 47, 44 and $43{\mu}M$, respectively. Culturing cells with diosgenin treatment caused down-regulation of hTERT expression. Discussion: These results show that diosgenin inhibits telomerase activity by down-regulation of hTERT gene expression in the A549 lung cancer cell line.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.616-624
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• 2022

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC₅₀ of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC₅₀ of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.

• Journal of Animal Science and Technology
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• v.45 no.2
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• pp.319-326
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• 2003

Angiotensin-I converting enzyme(ACE)inhibitor was isolated from beef by-products. The beef by- product hydrolysates prepared with various proteases were tested for the inhibitory effects against ACE. The proteases used were proteinase A from bakers yeast, protease type ⅩIII fungal and thermolysin. The maximum inhibitory effect was observed after hydrolysis for 12hrs(beef heart) and 24hrs(beef spleen), respectively. After gel filtration, IC50 value was 0.37mg/ml in beef heart and 1.84mg/ml in beef spleen. After RP-HPLC, the IC50 value of peak 1, peak 2, peak 3 and peak-4 were 0.28mg/ml, 0.26mg/ml, 0.25mg/ml and 0.35mg/ml, respectively. In the results of amino acid composition of peak 1, peak 2, peak 3 and peak 4, it was observed that peak 1 was consisted mainly of glycine and methionine, peak 2 was proline, cystine and methionine, peak 3 was proline and peak 4 was alanine, methionine and leucine. In conclusion, beef heart hydrolysate treated with thermolysin+ proteinase A was shown to have the highest inhibitory effect for 12hrs incubation at 37$^{\circ}C$.

• Korean Journal of Plant Resources
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• v.25 no.2
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• pp.232-239
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• 2012

A laboratory experiment was conducted to determine the content of phenolics and flavonoids, antioxidant activity and cytotoxicity from methanol extracts of different plant parts of $T.$ $officinale$ F. H. Wigg. Total phenolics [mg chlorogenic acid equivalents (FAE) $kg^{-1}$ DW] was highest in flower extracts (72.0 mg $kg^{-1}$), followed by leaf, root, and stalk extracts of $T.$ $officinale$ ($p$ < 0.05). The result of total flavonoid level [mg naringin equivalents $kg^{-1}$ DW] had same tendency to differential total phenolics contents among plant parts, but showed lower ranges of amount. The antioxidant activity of the methanol extracts from all the plant parts dose-dependently increased. DPPH (1,1-diphenyl-2-picryl hydrazyl radical) free radical scavenging activity was highest in flower extracts ($IC_{50}$ value = 624.3 mg $kg^{-1}$ ), and followed by leaf, root, and stalk extracts of $T.$ $officinale$ ($p$ < 0.05). By means of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, cell viability of Calu-6 for human pulmonary carcinoma and SNU-601 for human gastric carcinoma showed the lowest $IC_{50}$ value in the flower extracts ($IC_{50}$ value = 85.7 and 311.4 mg $kg^{-1}$, respectively), indicating the highest cytotoxicity. The results suggested that total phenolics content and total flavonoids level in different plant parts of $T.$ $officinale$ were highly correlated with antioxidative ($r^2$=0.7280 to 0.9971) or with cytotoxic activities ($r^2$=0.5795 to 0.9515).

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.6
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• pp.864-871
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• 2010

White and black garlic pastes were fermented by Leuconostoc mesenteroides and evaluated for its rheological and functional properties such as consistency, antioxidant and angiotensin converting enzyme inhibitory activity. The pH, acidity and solid content of black garlic paste were 4.60, 1.23%, 22.63%, respectively. The viable cell counts and consistency of fermented garlic was decreased by adding higher amounts of black garlic paste. Fermentation of white garlic (40%)/black garlic (10%) showed viable cell counts of $1.6\times10^{11}$, fluid consistency of 9.31 $Pa{\cdot}s^n$. Water and 70% ethanol extract from fermented garlic showed the polyphenol content of 6.29mg/mL and 5.99 mg/mL, respectively. Also, water extract indicated the DPPH radical scavenging effects and angiotensin converting enzyme (ACE) inhibitory activity with $IC_{50}$ 1.03 mg/mL and $IC_{50}$ 68.54 mg/mL, respectively. ACE inhibitory activity was increased with adding black garlic paste. Conversion of sucrose into dextran polymer in fermented garlic was drastically decreased by the addition of black garlic paste, indicating from 85% (0% black garlic) to 20% (20% black garlic) conversion yield. Garlic paste fermented with 10% black/40% white garlic showed the decrease in consistency and viable cell counts during both cold and freezing storages. In particular, consistency of fermented garlic was lower during freezing storage than cold storage, and the viable cell counts was drastically decreased after storage for 2 weeks.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.9
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• pp.1369-1373
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• 2003

ACE (Angiotensin-I converting enzyme) inhibitory peptides derived from foods are thought to suppress high blood pressure by inhibiting ACE. We tried to make efficient production of the ACE inhibitory hydrolysate from egg albumen. A hydrolysate digested by neutrase presented the highest ACE inhibitory activity ($IC_50\;value=256.35{\mu}g/ml$) and the proper proteolysis was occurred by 1.0% enzyme addition and 4 h incubation at $47^{\circ}C$. Antihypertensive effect of neutrase hydrolysate was investigated in spontaneously hypertensive rats (SHR, n=5). Systolic blood pressure (SBP) was decrease by 6.88% (-14.14 mmHg, p<0.05) at 3 h after oral administration of 300 mg/kg body weight, and by 13.33% (-27.72 mmHg, p<0.05) by emulsified hydrolysate. These results showed that it is very effective to utilize egg albumen as a protein source for the production of ACE inhibitory peptides. However, further studies are required to investigate the methods to increase recovery yield and the isolation of active peptide is necessary for determining its sequence responsible for ACE inhibitory activity.

• Korean Journal of Plant Resources
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• v.28 no.3
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• pp.312-320
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• 2015

Total phenol, flavonoid and antioxidant components of cabbage leaf samples derived from different cultivar were determined. Total phenol compound content showed the highest amount in methanol extracts from ‘YR Howol’ cultivar (11.72 ㎎/g), followed by ‘Harutame’ (10.66㎎/g), ‘Winstar’ (10.34 ㎎/g) and YR Hero (10.20 ㎎/g). The highest amount of total flavonoid content was observed from the methanol extracts of Harutame (5.39 ㎎/g), followed by Winstar (4.28 ㎎/g), Wialhowol (4.10 ㎎/g). The SOD enzyme activity showed a high activity of ‘YR Hogeo’ cultivar, and the cultivar of ‘YR Howol’ cultivar showed the lowest activity of SOD. The activity of CAT and APX showed higher values ‘Ogane’ and ‘YR Hogeol’ cultivars than the other cultivars. The POD activities showed relatively high values ‘Ogane’ and ‘YR Howol’ cultivars compared with other cultivars. The free radical (DPPH) scavenging activity showed lower IC₅₀ values of ‘Harutame’ (15.71) and ‘YR Howol’ cultivar (16.88), however methanol extract of ‘YR Hero’ cultivar (22.49) being the highest. The extracts of all cabbage cultivars in the reaction solution of pH 1.2 could be decomposed nitrite more than 50%. Especially, the cultivar ‘YR Hogeol’ and ‘Ogane’ showed a relatively high nitrite scavenging activity for each 60.13% and 57.20% respectively. The IC₅₀ values of antioxidant activity determined by ABTS were lower in ‘Harutame’ (17.04) and ‘YR Howol’ cultivar (17.97), and its results observed similar with values obtained from the same extracts by DPPH method. The result of this study suggests that the methanol extract of Brassica oleracea L. contains the high amount of phenolic and higher radical scavenging activities.

• Korean Journal of Environmental Biology
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• v.22
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• pp.54-62
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• 2004

We examined the impacts of anthyopogenic pollutant (benzo〔a〕pyrene) on the growth and photosynthesis of five marine phytoplankton species (Skeletonema costatum, Heterosigma akashiwo, Prorocentrum dentatum, P. minimum, Aknshiwo sanguinea), which are dominant in Korean coastal water. After the 72 h exposure to benzo〔a〕pyrene, the dramatic decrease in cell numbers was observed in the range of 1 to 10 $\mu\textrm{g}$ L$^{-1}$ for S. costatum, P. minimum, P. dentatum, whereas for A. sanguinea and H. akashiwo at the low concentrations 0.1 to 1 $\mu\textrm{g}$ L$^{-1}$ . Among the 5 phytoplankton species, the highest growth inhibition concentration ($IC_{50}$/) was 6.20 $\mu\textrm{g}$ L$^{-1}$ for P. minimum, followed by 2.14 $\mu\textrm{g}$ L$^{-1}$ for P. dentatum, 1.68 $\mu\textrm{g}$ L$^{-1}$ for S. costatum, 0.74 $\mu\textrm{g}$ L$^{-1}$ for H. akashiwo, 0.10 $\mu\textrm{g}$ L$^{-1}$ for A. sanguinea. The five species exposed to the low concentration of 1 $\mu\textrm{g}$ L$^{-1}$ were recovered after transferring to new media, but the species exposed to the high concentrations of 10 and 100 $\mu\textrm{g}$ L$^{-1}$ were not recovered, with the exception of P. minimum. Those results indicate that the thecate dinoflagellate P. minimum is most tolerant to the chemical and the athecate dinoflagellate A. sanguinea is not. Geneyally, the cell-specific photosynthetic capacity of H. akashiwo exposed to the low concentrations of 0.1 and 1 $\mu\textrm{g}$ L$^{-1}$ was higher than that of the cells in the control, whereas the cells exposed to the high concentrations of 5 and 10 $\mu\textrm{g}$ L$^{-1}$ showed the negligible photosynthetic level by the first few days of the experiment. In the case of the cells exposed to the concentration of 5 $\mu\textrm{g}$ L$^{-1}$ , after 12 days of the experiment the photosynthetic capacity was increased toward the end of the experiment. This indicates that H. akashiwo may utilize the benzo〔a〕pyrene as a carton source for its growth when exposed to low concentrations. Results suggest that anthropogenic pollutants such as benzo〔a〕pyrene may have significant influence on the succession of phytoplankton species composition and the primary production in coastal marine environments.