• Journal of Life Science
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• v.19 no.8
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• pp.1023-1032
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• 2009

Despite the fact that many cancer cells are sensitive to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, some cancer cells show either partial or complete resistance to TRAIL. Human leukemic K562 and CEM cells also show resistance to TRAIL-induced apoptosis. Novel molecular target and treatment strategies are required to overcome TRAIL resistance of human leukemia cells. Therefore, the purpose of this study was to target key anti-apoptotic molecules deciding TRAIL resistance for sensitization of TRAIL-resistant K562 and CEM cells, and to evaluate the effect of quercetin as a TRAIL sensitizer on these TRAIL-resistant cells. We found that quercetin acted in synergy with TRAIL to enhance TRAIL-induced apoptosis in K562 cells by inhibition of the DNA-PK/Akt signaling pathway, which leads to enhancement of TRAIL-mediated activation of caspases and concurrent cleavage of PARP and up-regulation of Bax. The findings suggest that the DNA-PK/Akt signaling pathway plays an essential role in regulating cells to escape from TRAIL-induced apoptosis, and quercetin could act in synergy with TRAIL to increase apoptosis by inhibition of the DNA-PK/Akt signaling pathway, which overcomes TRAIL-resistance of K562 and CEM cells. This study suggests that DNA-PK might interfere with TRAIL-induced apoptosis in human leukemic cells through activation of the Akt signaling pathway.

• Korean Journal of Applied Biomechanics
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• v.17 no.2
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• pp.157-166
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• 2007

This study was to compare the major kinematic factors between the success and failure group on performing the back somersault motion in floor exercise. Three gymnasts(height : $167.3{\pm}2.88cm$, age : $22.0{\pm}1.0years$, body weight : $64.4{\pm}2.3kg$) were participated in this study. The kinematic data was recorded at 60Hz with four digital video camera. Two successful motions and failure motions for each subject were selected for three dimensional analysis. 1. Success Trail It was appear that success trail was larger than failure group in projection velocity, but success trail was smaller than failure trail in projection angle. Also it was appear that success trail was longer than failure group in the time required. Hand segment velocity and maximum velocity in success trail were larger than those in failure trail, and this result was increasing the projection velocity and finally increasing the vertical height of center of mass. At the take-off(event 2), flection amount of hip and knee joint angle was contributed to the optimal condition for the take-off and at the peak point, hip and knee joint angle was maximum flexed for reducing the moment of inertia. Also in this point, upper extremities of success trail extended more than those of failure trail. in this base, success trail in upward phase(p3) 2. Failure Trail It was appear that failure trail was smaller than success trail in projection velocity, but failure trail was larger than success trail in projection angle. Also it was appear that failure trail was more short than success trail in the time required. Hand segment velocity and maximum velocity in failure trail were smaller than those in success trail, and this result was reducing the projection velocity and finally reducing the vertical high of center of mass. At the take-off(event 2), flection amount of hip and knee joint angle wasn't contributed to the optimal condition for the take-off and at the peak point, hip and knee joint angle wasn't maximum flexed for reducing the moment of inertia. Also in this point, upper extremities of failure trail didn't extended more than those of success trail.

• Journal of Agricultural Extension & Community Development
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• v.17 no.3
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• pp.587-606
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• 2010

Theme trail construction should be changed from existing form which connects line to line, or point to line. It should be developed into area form. The project of Trail construction must be converted in area form. The aggregate of the points which is a base element of walk is a line, and the harmonious connection of various line is the area. The close relationship with points and lines is important to operate the project of trail construction in area form effectively. Subject of the project of Theme trail construction of area form must become the village residents which are being contiguous in trail. They must operate management and about trail. The project of Trail construction of area form the plan making is established and if the subjects which, will operate and manage that place are decided upon according to theme must construct the trail of the wide area concept which connects the trail of that trail and neighborhood. If becomes like that local resident and the citizen will be able to coexist with mediation of Trail. If the project of Trail construction of village resident leading is propelled applying rural amenity resources in a way, the trail model which one phases advances could be presented for ecological, economical and cultural.

• Journal of Pharmaceutical Investigation
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• v.33 no.4
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• pp.261-265
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• 2003

Tumor necrosis facto-related apoptosis-inducing ligand (TRAIL) is a recently identified member of the tumor necrosis factor cytokine superfamily. TRAIL has been shown to induce apoptosis in a number of tumor cells whereas cells from most of normal tissues are highly resistant to TRAIL-induced apoptosis. These observations have raised considerable interest in the use of TRAIL in tumor therapy. In this study we report the biodistribution fates and serum expression pattern of plasmid DNA encoding TRAIL (pTRAIL) delivered in erythrocyte ghosts (EG). pTRAIL was loaded into EG by electroportion in a hypotonic medium The mRNA expression of pTRAIL was prolonged following delivery in EG-encapsulated forms. EG containing pTRAIL showed significant levels of mRNA expression in the blood over 9 days. The organ expression patterns of pTRAIL delivered via EG, however, did not significantly differ from those of naked pTRAIL, indicating that the expression-enhancing effect of EG containing pTRAIL was localized to the blood. These results suggest that pTRAIL-loaded EG might be of potential use in the treatment of hematological diseases such as TRAIL-sensitive leukemia.

• Journal of Life Science
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• v.19 no.9
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• pp.1209-1217
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• 2009

Many cancer cells are sensitive to the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. However, some cancer cells show either partial or complete resistance to TRAIL. Human colon carcinoma KM12 cells have been shown to be insensitive to TRAIL-induced apoptosis. To overcome TRAIL resistance in KM12 cells, we targeted key anti-apoptotic molecules involved in the modulation of TRAIL resistance in the cells, and evaluated the effects of quercetin as a TRAIL sensitizer in the cells. We found that quercetin acted in synergy with TRAIL to enhance TRAIL-induced apoptosis in KM12 cells by the down-regulation of c-FLIP and DNA-PKcs/Akt and up-regulation of death receptors (DR4/DR5), which led to the enhancement of TRAIL-mediated activation of caspases and subsequent cleavage of PARP, as well as up-regulation of Bax. These findings suggest that the DNA-PKcs/Akt signaling pathway, as well as c-FLIP, play essential roles in regulating cells in the escape from TRAIL-induced apoptosis. Based on these results, this study provides a potential application of quercetin in combination with TRAIL in the treatment of human colon cancer.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.62-67
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• 2012

TNF-related apoptosis-inducing ligand (TRAIL) is a promising agent for management of cancer because of its selective cytotoxicity to cancer cells. However, some cancer cells have resistance to TRAIL. Accordingly, novel treatment strategies are required to overcome TRAIL resistance. Here, we examined the synergistic apoptotic effect of apigenin in combination with TRAIL in Huh-7 cells. We found that combined treatment of TRAIL and apigenin markedly inhibited Huh-7 cell growth compared to either agent alone by inducing apoptosis. Combined treatment with apigenin and TRAIL induced chromatin condensation and the cleavage of poly (ADP-ribose) polymerase (PARP). In addition, enhanced apoptosis by TRAIL/apigenin combination was quantified by annexin V/PI flow cytometry analysis. Western blot analysis suggested that apigenin sensitizes cells to TRAIL-induced apoptosis by activating both intrinsic and extrinsic apoptotic pathway-related caspases. The augmented apoptotic effect by TRAIL/apigenin combination was accompanied by triggering mitochondria-dependent signaling pathway, as indicated by Bax/Bcl-2 ratio up-regulation. Our results demonstrate that combination of TRAIL and apigenin facilitates apoptosis in Huh-7 cells.

• Journal of Life Science
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• v.24 no.7
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• pp.769-776
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• 2014

Anisomycin, also known as flagecidin, is an antibiotic produced by Streptomyces griseolus that inhibits protein synthesis by binding to the ribosomal 28S subunit. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein that induces apoptotic cell death. TRAIL primarily causes apoptosis in tumor cells by binding to death receptors. Many human cancer cell lines are refractory to TRAIL-induced cell death. In this study, we investigated whether anisomycin could enhance TRAIL-mediated apoptosis in TRAIL-resistant human hepatocarcinoma Hep3B cells. Treatment with anisomycin and TRAIL alone did not reduce cell viability in Hep3B cells. However, in the presence of TRAIL, the anisomycin concentration dependently reduced the cell viability. Our results indicate that anisomycin sensitizes Hep3B cells to TRAIL-mediated apoptosis and that this occurs, at least partly, via caspase activation. Interestingly, Bid knockdown by small interfering RNA significantly reduced the induction of apoptosis in combination with anisomycin and TRAIL, indicating that anisomycin effectively acts to lower the threshold at which TRAIL-mediated truncated Bid triggers the mitochondrial-mediated apoptosis program in Hep3B cells. Therefore, the use of TRAIL in combination with anisomycin might provide an effective therapeutic strategy for the safe treatment of some TRAIL-resistant cancer cells.

• Journal of Life Science
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• v.21 no.11
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• pp.1641-1651
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• 2011

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) is a recently identified member of the TNF ligand family that can initiate apoptosis through the activation of their death receptors. TRAIL has been paid attention as a potential anti-cancer drug, because it selectively induces apoptosis in tumor cells in vitro and in vivo but not in most normal cells. However, recent studies have shown that some cancer cells including malignant renal cell carcinoma and hepatocellular carcinoma, are resistant to the apoptotic effects of TRAIL. Therefore, single treatment with TRAIL may not be sufficient for the treatment of various malignant tumor cells. Understanding the molecular mechanisms of TRAIL resistance and identification of sensitizers capable of overcoming TRAIL resistance in cancer cells is needed for the establishment of more effective TRAIL-based cancer therapies. Chemotherapeutic drugs induce apoptosis and the upregulation of death receptors or activation of intracellular signaling pathways of TRAIL. Numerous chemotherapeutic drugs have been shown to sensitize tumor cells to TRAIL-mediated apoptosis. In this study, we summarize biological agents and drugs that sensitize tumors to TRAIL-mediated apoptosis and discuss the potential molecular basis for their sensitization.

• Korean Journal of Agricultural Science
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• v.49 no.2
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• pp.367-377
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• 2022

The purpose of this study was to analyze the deterioration of trail conditions and to obtain information for desirable maintenance and restoration of a trail in Deogyusan National Park. The physical characteristics of a trail were surveyed at a total of 412 sites over 79.8 km length. The average trail degree and width were found to be 14.31° and 1.60 m, respectively, while the average bare trail width was 1.40 m and the average maxim trail depth was 5.66 cm. Major deterioration types of trail were trail deepening (36.6%), rock exposure (33.9%), and root exposure (12.5%) in order of frequency. Deterioration classes of the trail were 0.626 km (0.8%), 3.110 km (3.9%) and 8.935 km (11.2%) for heavily, moderately, and lightly deteriorated, respectively, with a deterioration rate of 12.671 km (15.9%). Compared to other national parks, the ratio damaged trail to the total trail was 15.9%, which is slightly higher than other, including Jirisan National Park 9.6% (2019), Bukhansan National Park 13.6% (2019), Sokrisan National Park 11.7% (2019), Chiaksan National Park 12.3% (2015), and Woraksan National Park 10.5% (2015). The section of trail in Deokyusan National Park where the damage grade is analyzed as "Heavy" should therefore be restored in consideration of the field conditions. In particular, the damage status of the trail is expected to be greatly improved when the trail surface maintenance level is restored.

• Journal of Life Science
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• v.26 no.4
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• pp.431-438
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• 2016

The tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer agent due to its unique ability to induce cancer cell death having only negligible effects on normal cells. However, many cancer cells tend to be resistant to TRAIL. In this study, we investigated the effects and molecular mechanisms of sodium butyrate (SB), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in 5637 human bladder cancer cells. Our results indicated that co-treatment with SB and TRAIL significantly increased the apoptosis induction, compared with treatment with either agent alone. Co-treatment with SB and TRAIL effectively increased the cell-surface expression of death receptor (DR) 5, but not DR4, which was associated with the inhibition of cellular Fas-associated death domain (FADD)-like interleukin-1β-converting enzyme (FLICE) inhibitory protein (c-FLIP). Furthermore, the activation of caspases (caspase-3, -8 and -9) and degradation of poly(ADP-ribose) were markedly increased in 5637 cells co-treated with SB and TRAIL; however, the synergistic effect was perfectly attenuated by caspase inhibitors. We also found that combined treatment with SB and TRAIL effectively induced the expression of pro-apoptotic Bax, cytosolic cytochrome c and cleave Bid to truncated Bid (tBid), along with down-regulation of anti-apoptotic Bcl-xL expression. These results collectively suggest that a combined regimen of SB plus TRAIL may offer an effective therapeutic strategy for safely and selectively treating TRAIL-resistant bladder cancer cells.