• Title/Summary/Keyword: SW480

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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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    • v.16 no.12
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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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    • v.53 no.4
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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
    • Korean Journal of Plant Resources
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    • v.28 no.3
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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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    • v.23 no.4
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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.

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

  • Shin, Hyeon-Jun;Lee, Joo-Heung
    • Journal of IKEEE
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    • v.24 no.1
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    • pp.186-193
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    • 2020
  • In this paper, we propose a multi-threading system to support reconfigurable hardware accelerators on Zynq SoC. We implement high-performance JPEG decoder with reconfigurable 2D IDCT hardware accelerators to achieve maximum performance available on the platform. In this system, up to four reconfigurable hardware accelerators synchronized with SW threads can be dynamically reconfigured to provide adaptive computing capabilities according to the given image resolution and the compression ratio. JPEG decoding is operated using images with resolutions 480p, 720p, 1080p at the compression ratio of 7:1-109:1. We show that significant performance improvements are achieved as the image resolution or the compression ratio increase. For 1080p resolution, the performance improvement is up to 79.11 times with throughput speed of 99 fps at the compression ratio 17:1.

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

  • Park, In-Soon
    • Environmental Mutagens and Carcinogens
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    • v.22 no.3
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    • pp.137-141
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    • 2002
  • The SNF2/SW12 family comprises proteins from a variety of species with in vivo functions, such as transcriptional regulation, maintenance of chromosome stability during mitosis, and various types of DNA repair. This study was shown the characterization of hrp2+ gene which was isolated by PCR amplification using the conserved domain of SNF2 motifs. Sequence analysis of hrp2+ gene showed striking evolutionary conservation among the SNF2 family of proteins. The transcript of hrp2+ gene was found to be a 4.7 kb as identified by Northern hybridization. In addition, to determine the transcription initiation site of hrp2+ gene, primer extension analysis was performed. This result showed the band of 64 bp. The transcriptional start point was mapped to a position of 47 base pair from the first ATG codon of translational initiation codon. In order to investigate the inducibility of hrp2+ gene, transcript levels were examined after treating the cells to various DNA damaging agents. The transcripts of hrp2+ were induced by UV-irradiation. But the transcripts were not induced by treatment of 0.25% Methylmethane sulfonate (MMS). These results implied that the effects of damaging agents are complex and different regulatory pathways exist for the induction of this gene.

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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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    • v.3 no.3
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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
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.10a
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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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Safety study on Genetic Toxicity of Cervi Pantotrichum Cornu Herbal acupuncture Solution(CPCHA) (유전독성시험에 의한 녹용약침의 안전성 연구)

  • Seo, Bu-Il;Byun, Boo-Hyeong
    • The Korea Journal of Herbology
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    • v.20 no.2
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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
    • Biomedical Science Letters
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    • v.17 no.1
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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.