• Title, Summary, Keyword: TRAIL

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Quercetin Sensitizes Human Leukemic Cells to TRAIL-induced Apoptosis: Involvement of DNA-PK/Akt Signal Transduction Pathway (Quercetin 에 의한 사람백혈병 세포의 TRAIL 에 대한 감수성 증가: DNA-PK/Akt 신호전달경로의 관여)

  • Park, Jun-Ik ;Kim, Mi-Ju;Kim, Hak-Bong;Bae, Jae-Ho;Lee, Jea-Won;Park, Soo-Jung;Kim, Dong-Wan;Kang, Chi-Dug;Kim, Sun-Hee
    • 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.

Kinematical Analysis of the Back Somersault in Floor Exercise (마루운동 제자리 뒤공중돌기 동작의 운동학적 분석)

  • Chung, Nam-Ju
    • Korean Journal of Sport 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.

Theme Trail District Planning for the Regional Activation -Case study on project of Trail construction each of the government agencies- (지역 활성화를 위한 테마길 조성 방안 -부처별 길 만들기 사업을 중심으로-)

  • Kim, Sang-Bum;Choi, Ja-Un;Jeong, Dae-Young;Kim, Eun-Ja
    • 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.

Prolonged Gene Expression Following Erythrocyte-Mediated Delivery of TRAIL Plasmid DNA (혈구세포 수송체로 투여된 트레일 유전자의 혈중 발현 지속 효과)

  • Byun, Hyang-Min;Kwon, Kyoung-Ae;Shin, Jee-Young;Oh, Yu-Kyoung
    • 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.

Quercetin Potentiates TRAIL-induced Apoptosis in Human Colon KM12 Cells (사람 대장암 KMl2세포에서 quercetin 의한 TRAIL이 유도하는 세포사멸의 증가)

  • Park, Jun-Ik;Kim, Hak-Bong;Kim, Mi-Ju;Lee, Jae-Won;Bae, Jae-Ho;Park, Soo-Jung;Kim, Dong-Wan;Kang, Chi-Dug;Kim, Sun-Hee
    • 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.

Apigenin Sensitizes Huh-7 Human Hepatocellular Carcinoma Cells to TRAIL-induced Apoptosis

  • Kim, Eun-Young;Kim, An-Keun
    • 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.

Anisomycin, an Inhibitor of Protein Synthesis, Overcomes TRAIL Resistance in Human Hepatocarcinoma Cells via Caspases Activation and Bid Downregulation (Caspase 활성 및 Bid의 발현 저하를 통한 단백질 생성 억제제인 anisomycin의 인체간암세포에서 TRAIL 매개 apoptosis 유발의 활성화)

  • Jin, Cheng-Yun;Park, Cheol;Hong, Su Hyun;Choi, Yung Hyun
    • 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.

Multiple Molecular Targets of Sensitizers in Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL/Apo2L)-Mediated Apoptosis (TRAIL 매개의 세포사멸 유도를 위한 다양한 분자적 타깃)

  • Min, Kyoung-Jin;Kwon, Taeg-Kyu
    • 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.

Status of Damage and Restoration Planning of Forest Trail in Choansan(Mt.) Neighborhood Park, Seoul, South Korea (초안산근린공원 숲길 훼손 실태 및 복원방안 연구)

  • Han, Bong-Ho;Ki, Kyong-Seok;Noh, Tai-Hwan
    • Korean Journal of Environment and Ecology
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    • v.26 no.6
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    • pp.923-933
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    • 2012
  • The purpose of this study targeting Choansan(Mt.) Neighborhood Park in Seoul of South Korea, whose level of visitation and use pressure has been recently increasingly high, was to understand distribution and damage status of forest trail and accordingly, set up direction of how to improve forest trail in urban area. With regards to current damage on forest trail in Choansan(Mt.) Neighborhood Park, the damaged trail with road width of over 2m and with erosion depth of over 30cm amounted to 20.3% and 36.3% respectively. And the trail section with bare land erosion, root exposure or rock exposure and the section whose impact rating class exceeded IV occupied 47.0% and 70.6%, indicating the forest trail was severely damaged. The severely injured trail route mainly included the main forest trail formed along the main ridge, the byroad connected to the main forest trail and the steep forest trail in low-lying area. Based on the study results, five types of restoration of forest trail in Choansan(Mt.) Neighborhood Park were offered, including prevention of forest trail extension, stabilization of forest trail base, maintenance of forest trail surface, vegetation restoration after closing forest trail and maintenance. Ecological restoration was additionally offered. The prevention of forest trail extension was planned to prevent expanded width of forest trail where bare land was exposed. The stabilization of forest trail base was planned to prevent erosion in the forest trail and exposure of roots. The maintenance of forest trail surface was planned in a way to protect the severely damaged forest trail surface by using wood deck and wood stairs and surfacing the road.

Sanguinarine Increases Sensitivity of Human Gastric Adenocarcinoma Cells to TRAIL-mediated Apoptosis by Inducing DR5 Expression and ROS Generation (AGS 인체 위암세포에서 DR5의 발현 및 ROS 생성의 증가를 통한 sanguinarine과 TRAIL 혼합처리의 apoptosis 유도 활성 촉진)

  • Lee, Taek Ju;Im, Yong Gyun;Choi, Woo Young;Choi, Sung Hyun;Hwang, Won Deok;Choi, Yung Hyun
    • Journal of Life Science
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    • v.24 no.9
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    • pp.927-934
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    • 2014
  • Sanguinarine, a benzophenanthridine alkaloid originally derived from the root of Sanguinaria canadensis, has been shown to possess antimicrobial, antioxidant, and anti-cancer properties. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer cells, but not most normal cells and has shown efficacy in a phase 2 clinical trial, development of resistance to TRAIL by tumor cells is a major roadblock. Our previous study indicated that treatment with TRAIL in combination with subtoxic concentrations of sanguinarine sensitized TRAIL-mediated apoptosis in TRAIL-resistant human gastric carcinoma AGS cells; however, the detailed mechanisms are not fully understood. In this study, we show that sanguinarine sensitizes AGS cells to TRAIL-mediated apoptosis as detected by MTT assay, agarose gel electrophoresis, chromatin condensation and flow cytometry analysis. Combined treatment with sanguinarine and TRAIL effectively induced expression of death receptor (DR) 5 but did not affect expression of DR4 and mitogen activated protein kinases signaling molecules. Moreover, the combined treatment with sanguinarine and TRAIL increased the generation of reactive oxygen species (ROS); however, N-acetylcysteine, ROS scavenger, significantly recovered growth inhibition induced by the combined treatment. Taken together, our results indicate that sanguinarine can potentiate TRAIL-mediated apoptosis through upregulation of DR5 expression and ROS generation.