• 제목/요약/키워드: SW-480

검색결과 67건 처리시간 0.023초

Aldose Reductase Inhibitor Fidarestat as a Promising Drug Targeting Autophagy in Colorectal Carcinoma: a Pilot Study

  • Pandey, Saumya
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권12호
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    • pp.4981-4985
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    • 2015
  • Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Targeting autophagic cell death is emerging as a novel strategy in cancer chemotherapy. Aldose reductase (AR) catalyzes the rate limiting step of the polyol pathway of glucose metabolism; besides reducing glucose to sorbitol, AR reduces lipid peroxidation-derived aldehydes and their glutathione conjugates. A complex interplay between autophagic cell death and/or survival may in turn govern tumor metastasis. This exploratory study aimed to investigate the potential role of AR inhibition using a novel inhibitor Fidarestat in the regulation of autophagy in CRC cells. Materials and Methods: For glucose depletion (GD), HT-29 and SW480 CRC cells were rinsed with glucose-free RPMI-1640, followed by incubation in GD medium +/- Fidarestat ($10{\mu}M$). Proteins were extracted by a RIPA-method followed by Western blotting ($35-50{\mu}g$ of protein; n=3). Results: Autophagic regulatory markers, primarily, microtubule associated protein light chain (LC) 3, autophagy-related gene (ATG) 5, ATG 7 and Beclin-1 were expressed in CRC cells; glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was used as an internal reference. LC3 II (14 kDa) expression was relatively high compared to LC3A/B I levels in both CRC cell lines, suggesting occurrence of autophagy. Expression of non-autophagic markers, high mobility group box (HMG)-1 and Bcl-2, was comparatively low. Conclusions: GD +/- ARI induced autophagy in HT-29 and SW-480 cells, thereby implicating Fidarestat as a promising therapeutic agent for colorectal cancer; future studies with more potent ARIs are warranted to fully dissect the molecular regulatory networks for autophagy in colorectal carcinoma.

Expression and in vitro function of anti-cancer mAbs in transgenic Arabidopsis thaliana

  • Song, Ilchan;Kang, Yang Joo;Kim, Dae Heon;Kim, Mi Kyung;Ko, Kisung
    • BMB Reports
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    • 제53권4호
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    • pp.229-233
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    • 2020
  • The anti-colorectal cancer monoclonal antibody CO17-1A (mAb CO), which recognizes the tumor-associated antigen EpCAM, was expressed in transgenic Arabidopsis plants. PCR and western blot analyses showed the insertion and expression of heavy chain (HC)/HC fused to the KDEL ER retention modif (HCK) and light chain (LC) of mAb CO and mAb CO with HCK (mAb COK) in Arabidopsis transformants. Both plant-derived mAbP CO and mAbP COK were purified from a biomass of approximately 1,000 seedlings grown in a greenhouse. In sandwich ELISA, both mAbP CO showed a slightly higher binding affinity for the target, EpCAM, compared to mAbM CO. In cell ELISA, both mAbsP COs showed binding affinity to the human colorectal cancer cell line SW480. Furthermore, mAbM CO, mAbP CO, and mAbP COK exhibited dose and timedependent regression effects on SW480 cells in vitro. In summation, both mAbP CO and mAbP COK, expressed in Arabidopsis, recognized the target antigen EpCAM and showed anti-proliferative activity against human colorectal cancer cells.

Anti-Cancer Activity of the Flower Bud of Sophora japonica L. through Upregulating Activating Transcription Factor 3 in Human Colorectal Cancer Cells

  • Lee, Jin Wook;Park, Gwang Hun;Eo, Hyun Ji;Song, Hun Min;Kim, Mi Kyoung;Kwon, Min Ji;Koo, Jin Suk;Lee, Jeong Rak;Lee, Man Hyo;Jeong, Jin Boo
    • 한국자원식물학회지
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    • 제28권3호
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    • pp.297-304
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    • 2015
  • The flower buds of Sophora japonica L (SF), as a well-known traditional Chinese medicinal herb, have been used to treat bleeding-related disorders such as hematochezia, hemorrhoidal bleeding, dysfunctional uterine bleeding, and diarrhea. However, no specific anti-cancer effect and its molecular mechanism of SF have been described. Thus, we performed in vitro study to investigate if treatment of SF affects activating transcription factor 3 (ATF3) expression and ATF3-mediated apoptosis in human colorectal cancer cells. The effects of SF on cell viability and apoptosis were measured by MTT assay and Western blot analysis against cleaved poly (ADP-ribose) polymerase (PARP). ATF3 activation induced by SF was evaluated using Western blot analysis, RT-PCR and ATF3 promoter assay. SF treatment caused decrease of cell viability and increase of apoptosis in a dose-dependent manner in HCT116 and SW480 cells. Exposure of SF activated the levels of ATF3 protein and mRNA via transcriptional regulation in HCT116 and SW480 cells. Inhibition of extracellular signal-regulated kinases (ERK) 1/2 by PD98059 and p38 by SB203580 attenuated SF-induced ATF3 expression and transcriptional activation. Ectopic ATF3 overexpression accelerated SF-induced cleavage of PARP. These findings suggest that SF-mediated apoptosis may be the result of ATF3 expression through ERK1/2 and p38-mediated transcriptional activation.

Anti-Proliferative Effect of Naringenin through p38-Dependent Downregulation of Cyclin D1 in Human Colorectal Cancer Cells

  • Song, Hun Min;Park, Gwang Hun;Eo, Hyun Ji;Lee, Jin Wook;Kim, Mi Kyoung;Lee, Jeong Rak;Lee, Man Hyo;Koo, Jin Suk;Jeong, Jin Boo
    • Biomolecules & Therapeutics
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    • 제23권4호
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    • pp.339-344
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    • 2015
  • Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. However, more detailed mechanism by which NAR exerts anti-cancer properties still remains unanswered. Thus, in this study, we have shown that NAR down-regulates the level of cyclin D1 in human colorectal cancer cell lines, HCT116 and SW480. NAR inhibited the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. Inhibition of proteasomal degradation by MG132 blocked NAR-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with NAR. In addition, NAR increased the phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine blocked cyclin D1 downregulation by NAR. p38 inactivation attenuated cyclin D1 downregulation by NAR. From these results, we suggest that NAR-mediated cyclin D1 downregulation may result from proteasomal degradation through p38 activation. The current study provides new mechanistic link between NAR, cyclin D1 downregulation and cell growth in human colorectal cancer cells.

Zynq SoC에서 재구성 가능한 하드웨어 가속기를 지원하는 멀티쓰레딩 시스템 설계 (Multi-threaded system to support reconfigurable hardware accelerators on Zynq SoC)

  • 신현준;이주흥
    • 전기전자학회논문지
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    • 제24권1호
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    • pp.186-193
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    • 2020
  • 본 논문에서는 Zynq SoC 환경에서 재구성 가능한 하드웨어 가속기를 지원하는 멀티쓰레딩 시스템을 제안한다. 압축된 정지 영상의 픽셀 데이터를 복원하는 고성능 JPEG 디코더를 구현하고 2D-IDCT 함수를 재구성 가능한 하드웨어 가속기로 설계하여 성능을 검증한다. 구현된 시스템에서 최대 4개의 재구성 가능한 하드웨어 가속기는 소프트웨어 쓰레드와 동기화되어 연산을 수행할 수 있으며 이미지 해상도와 압축률에 따라 다른 성능 향상을 보인다. 1080p 해상도 영상의 경우 17:1의 압축률에서 최대 79.11배의 성능 향상과 99fps의 throughput 속도를 보여준다.

Schizosaccharomyces pombe에서 SNF2에 속하는 hrp2+ 유전자의 특성 연구 (Characterization of hrp2 + Gene Related to SNF2 Family in Schizosaccharomyces pombe)

  • Park, In-Soon
    • 한국환경성돌연변이발암원학회지
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    • 제22권3호
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    • pp.137-141
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    • 2002
  • 본 연구는 분열형 효모 Schizosaccharomyces pombe에서 여러 가지 DNA 절제회복 및 유전자 발현에 관여하는 SNF2/SW12유전자의 기능을 연구하기 위하여 이에 관련되는 유전자를 분리하고 그 특성을 연구하였다. SNF2 motif 의 conserved sequence를 primer로 하여 중합효소 연쇄반응(PCR) 방법으로 480 bp 크기의 DNA fragment를 분리하여, 이를 probe로 하여 효모에서 hrp2+ 유전자를 분리하였다. 분리한 hrp2+ 유전자의 sequence homology를 비교한 결과 3개의 SNF2 motif를 포함하고 있었다. hrp2+유전자의 전사체 크기는 4.7 kb임을 Northern hybridization으로 확인하였다. hrp2+유전자의 전사 개시 부위를 알기 위하여 primer extension분석을 한 결과, 첫 번째 ATG에서 약47 base pair 위쪽에 위치함을 확인하였다. 또한 특성 연구를 위하여 Northern hybridization으로 hrp2+ 유전자의 UV와 MMS에 대한 유도성을 조사한 결과 자외선에 대해서만 유전자의 발현이 유도되었다. 이 결과 분리한 hrp2+는 UV-inducible 유전자임을 확인하였다.

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Studies on Antimutagenic and Cytotoxic Effects of Seaweeds Protein-Polysaccharides

  • Lee, Yong-Kyu;Jung, Sook-Hyun
    • Preventive Nutrition and Food Science
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    • 제3권3호
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    • pp.272-276
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    • 1998
  • Polysaccharide content in protein-polysaccharides (PPS) extracted from sea mustard, sea tangle and fusiform were 40.61, 38.42 and 52.80% , respectively. 5% of sea tangle PPS showed highest inhibitory activity on 4-nitorquinoline -1-oxide(4-NQO) against Salmonella typhimurium TA100 compared to the other seaweed PPS. 5% of sea mustard PPS showed highest inhibition ration of 62% on 2-nitrofluorene(2-NF)against Salmonella typhimurium TA98. These PPS extracts showed cytotoxic activity against human colon cancer cell (SW-480), and showed mild cytotoxic activity on human stomach cancer cell(SNU-1) and human hepatic cancer cell(HepG 2).

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Anticancer Activity of Sageretia theezans in Human Colorectal Cancer Cells

  • Kim, Ha Na;Park, Su Bin;Kim, Jeong Dong;Jeong, Hyung Jin;Jeong, Jin Boo
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2018년도 추계학술대회
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    • pp.108-108
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    • 2018
  • In this study, we evaluated the anti-cancer effect of extracts of leaves (ST-L) and branches (ST-B) from Sageretia theezans in human colorectal cancer cells. ST-L and ST-B significantly inhibited the proliferation of human colorectal cancer cells, SW480. ST-L and ST-B decreased cyclin D1 protein level through the induction of cyclin D1 proteasomal degradation via $GSK3{\beta}$-dependent threonine-286 phosphorylation of cyclin D1. In addition, ST-L and ST-B increased HO-1 protein through p38, ROS and $GSK3{\beta}$-dependent Nrf2 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-cancer drug to treat human colorectal cancer.

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유전독성시험에 의한 녹용약침의 안전성 연구 (Safety study on Genetic Toxicity of Cervi Pantotrichum Cornu Herbal acupuncture Solution(CPCHA))

  • 서부일;변부형
    • 대한본초학회지
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    • 제20권2호
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    • pp.1-6
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    • 2005
  • Objectives : The purpose of this study is to investigate genetic toxicity of Cervi pantotrichum Cornu herbal acupuncture solution(CPCHA). Methods : In this study, a series of investigation have been carried out to analyze the effects of Cervi pantotrichum Cornu herball acupuncture solution(CPCHA) on colony forming ability of NIH3T3cells, Hela cells and adrenorectal coloncell for genetic toxicity test. Results and Conclusions : From the above results, it is suggested that Cervi pantotrichum Cornu herball acupuncture solution(CPCHA) was limited 0.5-10ug/ml by test. Cervi pantotrichum Cornu herball acupuncture solution(CPCHA) did not exert the protective role to the genetic toxicity in kinds of cell lines used in this study. From these results, Cervi pantotrichum Cornu herbal aqua-acupuncture solution needs further study to prove it's function in cell culture system.

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Licochalcone A, a Major Phenolic Constituent of Glycyrrhiza inflata, Suppresses Angiogenin Expression in Colon Cancer Cells

  • Kim, Jin-Kyung
    • 대한의생명과학회지
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    • 제17권1호
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    • pp.85-88
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    • 2011
  • Tumor angiogenesis, which is essential for tumor growth and tumor metastasis, depends on angiogenic factors produced by tumor cells and/or infiltrating cells such as endothelial cells and immune cells in tumor tissue. Previously, we reported that licochalcone A (LicA), an important bioactive compound of Glycyrrhiza inflate, suppresses angiogenesis, tumor growth and metastasis. In this study, we evaluated the effect of LicA on angiogenin production in colon cancer cells because angiogenin is an essential factor to regulate angiogenesis and tumor progression. When we examined the angiogenin levels in three human colon cancer cells, HT-29, SW480 and Caco-2, LicA treatment significantly reduced the amounts of angiogenin among three cancer cell lines. In an in vivo study in which mice were implanted with HT-29 cells, oral administration of LicA reduced angiogenin in tumor tissues when compared with vehicle-administered mice. These results suggest that reduced angiogenin in response to LicA treatment may play essential role to inhibit tumor growth, angiogenesis as well as metastasis.