• Title/Summary/Keyword: p53-p21 system

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Induction of Cell Cycle Arrest at G2/M phase by Ethanol Extract of Scutellaria baicalensis in Human Renal Cell Carcinoma Caki-1 Cells (황금 에탄올 추출물에 의한 인간 신장암 세포주 Caki-1의 G2/M arrest 유발)

  • Park, Dong-Il;Jeong, Jin-Woo;Park, Cheol;Hong, Su-Hyun;Shin, Soon-Shik;Choi, Sung-Hyun;Choi, Yung-Hyun
    • Herbal Formula Science
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    • v.23 no.2
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    • pp.199-208
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    • 2015
  • Objectives : In the present study, we investigated the effects of ethanol extract of Scutellaria baicalensis (EESB) on the progression of cell cycle in human renal cell carcinoma Caki-1 cells. Methods : The effects of EESB on cell growth and apoptosis induction were evaluated by trypan blue dye exclusion assay and flow cytometry, respectively. The mRNA and protein levels were determined by Western blot analysis and reverse transcription-polymerase chain reaction, respectively. Results : It was found that EESB treatment on Caki-1 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death as detected by Annexin V-FITC staining. The flow cytometric analysis indicated that EESB resulted in G2/M arrest in cell cycle progression which was associated with the down-regulation of cyclin A expression. Our results also revealed that treatment with EESB increased the mRNA and proteins expression of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), without any noticeable changes in cyclin B1, Cdk2 and Cdc2. In addition, the incubation of cells with EESB resulted in a significant increase in the binding of p21 and Cdk2 and Cdc2. These findings suggest that EESB-induced G2/M arrest and apoptosis in Caki-1 cells is mediated through the p53-mediated upregulation of Cdk inhibitor p21. Conclusions : Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent and further studies will be needed to identify the biological active compounds that confer the anti-cancer activity of S. baicalensis.

Induction of Apoptosis by Methanol Extract of Gloiopeltis furcata in Human Leukemia Cell Line U937 (인체백혈병세포의 증식에 미치는 불등가사리 메탄올 추출물의 영향)

  • Choi, Woo Young;Park, Cheol;Kim, Gi Young;Lee, Won Ho;Bae, Song-Ja;Choi, Yung Hyun
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.2
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    • pp.76-83
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    • 2006
  • Epidemiological studies have indicated that the ubiquitous consumption of seaweeds is a protective factor against some types of cancer. Previous results showed that the administration of seaweed powder or extract reduced the incidence rate of chemically induced tumorigenesis using in vivo animal model. Recently, we reported that the extracts of Gloiopeltis furcata, a kind of Korean edible seaweed, caused he cell growth inhibition of various human cancer cell lines, among them methanol extract exhibited a relatively strong antiproliferative activity. However, the molecular mechanisms of this seaweed in malignant cells have been poorly studied until now. To elucidate this problem, we investigated the effects of methanol extract of G. furcata (MEGF) on the growth inhibition in several human cancer cell lines, and further we analyzed the effects of this extract were tested on the activity of apoptosis induction in human leukemic cells. The results demonstrated that MEGF treatment resulted in the morphological changes and the growth inhibition in a dose-dependent manner. Furthermore, MEGF potently suppresses the growth of human leukemic U937 cells by induction of apoptosis, which was associated with induction of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in a tumor suppressor p53-independent fashion and up-regulation of Fas/FasL system. Further studies will be needed to identify the active compounds that confer the anticancer activity of MEGF. Once such compounds are identified, the mechanisms by which they exert their effects can begin to be characterized.

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APPLICATION OF ACIDIC PRIMER FOR ORTHODONTIC ADHESIVE SYSTEM (Acidic primer를 이용한 교정용 브라켓 접착의 전단결합강도)

  • Kim, Jin-Hee;Jin, Hun-Hee;Oh, Jang-Kyun
    • The korean journal of orthodontics
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    • v.31 no.1 s.84
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    • pp.137-147
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    • 2001
  • Acidic primer is the bonding agent which combines the conditioning and priming agent into the single solution and was originally developed for the dentin bonding system. It is less harmful to the tooth structure and more convenient to manipulate than the traditional etching procedure. The Purpose of this study is to evaluate the shear bond strength of various bonding materials when the enamel is treated with acidic primer for the bracket bonding procedure. Fifty recently extracted human premolars were randomly separated into five groups -Group I using Clearfil Liner Bond 2 adhesive system to the enamel treated with acidic primer, Group II using Transbond XT adhesive system to the enamel treated with acidic primer, Group III using panavia 21 adhesive system to the enamel treated with acidic primer, Group IV using Fuji-Ortho LC adhesive system to the enamel treated with acidic primer, Group V using Transbond XT adhesive system to the enamel treated with 37$\%$ phosphoric acid. The shear bond strength was measured with Instron universal testing machine after storing in $37^{\circ}C$ water bath for 48 hours. After debonding, the teeth and brackets were examined under scanning electron microscope (SEM) and assessed with the adhesive remnant index (ARI). The results were as follows : 1. There were no significant differences in shear bond strength between group III ($8.69{\pm}2.72MPa$), group IV (9.7 ± 3.16 MPa), and group V ($10.48{\pm}2.60MPa$) (p>0.05). 2. The shear bond strength of group III and group IV was significantly higher than that of group I ($1.09{\pm}0.53MPa$), and Group II ($2.70{\pm}1.46MPa$) (p<0.05). 3. The ARI of group IV ($2.1{\pm}1.1$) and group V ($2.9{\pm}0.3$) was significantly higher than that of group I ($0.2{\pm}0.4$), group II ($0.3{\pm}0.9$) and group III ($0.2{\pm}0.4$) (p<0.05). 4. There were no significant difference between the ARI of group IV and group V (p>0.05). This result suggests that the combination of acidic primer and some bonding adhesive can provide sufficient shear bond strength for clinical orthodontics.

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CRM1 inhibitor S109 suppresses cell proliferation and induces cell cycle arrest in renal cancer cells

  • Liu, Xuejiao;Chong, Yulong;Liu, Huize;Han, Yan;Niu, Mingshan
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.2
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    • pp.161-168
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    • 2016
  • Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor effects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory effects of S109 on CRM1 is reversible. Our data demonstrated that S109 significantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the effects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy.

The Proteasome Inhibitor MG132 Sensitizes Lung Cancer Cells to TRAIL-induced Apoptosis by Inhibiting NF-κ Activation (폐암세포주에서 NFκ 활성 억제를 통한 Proteasome 억제제 MG132의 TRAIL-유도성 Apoptosis 감작 효과)

  • Seo, Pil Won;Lee, Kye Young
    • Tuberculosis and Respiratory Diseases
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    • v.65 no.6
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    • pp.476-486
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    • 2008
  • Background: TRAIL (TNF-related apoptosis inducing ligand) is a newly identified member of the TNF gene family which appears to have tumor-selective cytotoxicity due to the distinct decoy receptor system. TRAIL has direct access to caspase machinery and induces apoptosis regardless of p53 phenotype. Therefore, TRAIL has a therapeutic potential in lung cancer which frequently harbors p53 mutation in more than 50% of cases. However, it was shown that TRAIL also could activates $NF-{\kappa}B$ in some cell lines which might inhibit TRAIL-induced apoptosis. This study was designed to investigate whether TRAIL can activate $NF-{\kappa}B$ in lung cancer cell lines relatively resistant to TRAIL-induced apoptosis and inhibition of $NF-{\kappa}B$ activation using proteasome inhibitor MG132 which blocks $I{\kappa}B{\alpha}$ degradation can sensitize lung cancer cells to TRAIL-induced apoptosis. Methods: A549 (wt p53) and NCI-H1299 (null p53) lung cancer cells were used and cell viability test was done by MTT assay. Apoptosis was confirmed with Annexin V assay followed by FACS analysis. To study $NF-{\kappa}B$-dependent transcriptional activation, a luciferase reporter gene assay was used after making A549 and NCI-H1299 cells stably transfected with IgG ${\kappa}-NF-{\kappa}B$ luciferase construct. To investigate DNA binding of $NF-{\kappa}B$ activated by TRAIL, electromobility shift assay was used and supershift assay was done using anti-p65 antibody. Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation. Results: A549 and NCI-H1299 cells were relatively resistant to TRAIL-induced apoptosis showing only 20~30% cell death even at the concentration 100 ng/ml, but MG132 ($3{\mu}M$) pre-treatment 1 hour prior to TRAIL addition greatly increased cell death more than 80%. Luciferase assay showed TRAIL-induced $NF-{\kappa}B$ transcriptional activity in both cell lines. Electromobility shift assay demonstrated DNA binding complex of $NF-{\kappa}B$ activated by TRAIL and supershift with p65 antibody. $I{\kappa}B{\alpha}$ degradation was proven by western blot. MG132 completely blocked both TRAIL-induced $NF-{\kappa}B$ dependent luciferase activity and DNA binding of $NF-{\kappa}B$. Conclusion: This results suggest that inhibition of $NF-{\kappa}B$ can be a potentially useful strategy to enhance TRAIL-induced tumor cell killing in lung cancer.

Microsomal Mixed Function Oxidase and Lipid Peroxidation in Liver and Lung of Sterptozotocin-Induced Diabetic Rats (Streptozotocin 유발 당뇨쥐의 간장 및 폐조직에서의 Microsomal Mixed Function Oxidase System과 과산화지질 생성)

  • 이순재;김관유
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.25 no.1
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    • pp.21-26
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    • 1996
  • 본 연구는 streptozotocin 유발 당뇨쥐에서의 MFO계활성 변화 및 이에 지질과산화를 관찰하고자 체중이 140kg 내외의 Sprague-Dawley 종 흰쥐 숫컷을 대조군과 당뇨 유발 시험군으로 나누어 4주간 사육하였다. 당뇨군은 STZ로 당뇨를 유발시켰으며 당뇨 유발 6일후 쥐를 희생기켜 간조직 및 폐조직 microsome 중의 cytochrome $P_{450}$ 및 cytochrome $b_[5}$ 함량과 NADPH-cytochrome $P_{450}$ reductase 활성도를 측정하고 아울러 microsome내의 지질과산화물을 측정하여 다음과 같은 결과를 얻었다. 실험군간에 식이 섭취량은 차이가 없었으나, 체중 증가량과 식이 효율은 당뇨군이 STZ군에 비해 현저하게 감소하였다. 간장 및 폐조직의 무게는 대조군과 당뇨군간에 유의적인 차이는 없었다. 간조직 및 GP조직 중의 cytochrome $P_{450}$ 함량은 대조군에 비해 당뇨군이 150%, 175%씩 증가하였다. 간조직 및 폐조직 중의 cytochrome $b_{5}$은 대조군에 비해 당뇨군이 53%,116%씩 각각 증가하였다. 간조직에서의 NADPH-cytochrome $P_{450}$ reductase 활성은 당뇨군이 대조군에 비해 46% 증가하였으며, 폐조직에서는 75%증가하였다. 지질과산화물가는 당뇨군이 대조군에 비해 간족에서는 약 95% 높았으며 폐조직에서는 73%높았다. 이상의 결과에서 STZ 유발 당뇨쥐에서는 MFO system의 활성도가 대조군에 비해 현저하게 증가되고 지질과산화반응이 같으 srudgid이 촉진되었으며 폐조직에서도 간조직에서와 비슷한 경향이었다. 이러한 것은 당뇨군에서는 MFO system의 활성증가로 free radical 생성이 증가되고 그 결과 지질과산화가 촉진되었다고 볼 수 있다.

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The Effect of Organizational Efficacy, Self-efficacy, Nursing Professionalism on Organizational Commitment in General (종합병원간호사의 조직효능감, 자기효능감, 간호전문직이 조직몰입에 미치는 영향)

  • Kim Hyun Woo;Eun Hee Park
    • Journal of Industrial Convergence
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    • v.21 no.7
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    • pp.75-82
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    • 2023
  • The purpose of this study was designed to help the operation of the hospital organization through analysis of factors influencing organizational commitment of general hospital nurses. 129 nurses in general hospitals were targeted in G City. This study was conducted to analyze the effects of group efficacy, self-efficacy, and nursing professionals on organizational commitment. T-test, ANOVA, Pearson's correlation coefficient, Descriptive statistics and multiple regression were used. Stepwise regression analysis found that organizational commitment was affected by group efficacy(β=0.240, p =.003), nursing professionalism(β=0.229, p =.004) and daytime work(β=0.249, p =.003), The F statistic was 10.478 (p <.001). Therefore, in order to improve organizational commitment, it will be necessary to prepare communication programs and cooperation programs per unit to improve collective efficacy. In addition, it is necessary to improve the system, such as a system dedicated to night workers, so that the working hours of nurses in general hospitals can be maintained constant. In addition, it is necessary to develop a support program so that nursing professionals do not decrease due to disappointment in reality in the nursing field.

Genetic Variations of ABCC2 Gene Associated with Adverse Drug Reactions to Valproic Acid in Korean Epileptic Patients

  • Yi, Ji Hyun;Cho, Yang-Je;Kim, Won-Joo;Lee, Min Goo;Lee, Ji Hyun
    • Genomics & Informatics
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    • v.11 no.4
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    • pp.254-262
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    • 2013
  • The multidrug resistance protein 2 (MRP2, ABCC2) gene may determine individual susceptibility to adverse drug reactions (ADRs) in the central nervous system (CNS) by limiting brain access of antiepileptic drugs, especially valproic acid (VPA). Our objective was to investigate the effect of ABCC2 polymorphisms on ADRs caused by VPA in Korean epileptic patients. We examined the association of ABCC2 single-nucleotide polymorphisms and haplotype frequencies with VPA related to adverse reactions. In addition, the association of the polymorphisms with the risk of VPA related to adverse reactions was estimated by logistic regression analysis. A total of 41 (24.4%) patients had shown VPA-related adverse reactions in CNS, and the most frequent symptom was tremor (78.0%). The patients with CNS ADRs were more likely to have the G allele (79.3% vs. 62.7%, p=0.0057) and the GG genotype (61.0% vs. 39.7%, p=0.019) at the g.-1774delG locus. The frequency of the haplotype containing g.-1774Gdel was significantly lower in the patients with CNS ADRs than without CNS ADRs (15.8% vs. 32.3%, p=0.0039). Lastly, in the multivariate logistic regression analysis, the presence of the GG genotype at the g.-1774delG locus was identified as a stronger risk factor for VPA related to ADRs (odds ratio, 8.53; 95% confidence interval, 1.04 to 70.17). We demonstrated that ABCC2 polymorphisms may influence VPA-related ADRs. The results above suggest the possible usefulness of ABCC2 gene polymorphisms as a marker for predicting response to VPA-related ADRs.

Studies on the Improvement of Embryo Transfer Efficiency in Korean Cattle I. Effect of Embryo Conditions on Pregnancy Rate after Embryo Transfer (한우에서 수정란 이식의 효율 증진에 대한 연구 I. 수정란의 조건이 이식 후 수태율에 미치는 영향)

  • 김흥률;김덕임;원유석;김창근;정영채;이규승;서길웅;박창식
    • Journal of Embryo Transfer
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    • v.13 no.1
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    • pp.53-60
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    • 1998
  • This study was carried out to establish an effective system for embryo transfer techniques by analyzing several factors affecting in-vivo embryo transfer in Korean cattle. Embryos produced in-vivo were transferred into a total of 301 recipients. The results obtained in studies on the factors affecting pregnancy rate after embryo transfer by condition of embryos were as follow ; 1. The pregnancy rate of 301 recipients was 45.2% and higher with fresh embryos than with frozen embryos(63.5% : 21.4%, P<0.01). Embryos superovurated by FSH-P had slightly greater than by SUPER-OV in pragnancy rate, athough these were no difference between two treatments. 2. The pregnancy rates of transferred morulae and blastocysts showed no difference between fresh and frozen embryos(63.5% : 63~6% ; 20.0% : 25.8%). However, the pregnancy rates by quality of flesh and frozen embryos were significantly different(P<0~05). The pregnancy rates were outstandingly high in the grade A, B of fresh embryos(59.0~66.4%), and in the grade A of frozen embryos(43.6%). 3. The number of transferred embryos showed no difference in pregnancy rate, but when frozen embryos transferred, the pregnancy rate was slightly higher with two embryos than that with one embryo.

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Pesticide Degradation Activity of Several Isolates of Soil Bacteria and Their Identification (토양에서 분리한 수종 세균의 농약분해력 검정 및 동정)

  • Park, Kyung-Hun;Lee, Young-Kee;Lee, Su-Heon;Park, Byung-Jun;Kim, Chan-Sub;Choi, Ju-Hyeon;Uhm, Jae-Youl
    • The Korean Journal of Pesticide Science
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    • v.10 no.2
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    • pp.138-148
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    • 2006
  • Two bacteria were isolated from the continuously pesticide-used soil under plastic film house and upland condition. The degradation test of several pesticides by the selected bacteria, B59 and B71, were conducted. The degradation rates for 6 pesticides, procymidone, chlorothalonil, ethoprophos parathior, alachlor and pendimethalin, in medium by the isolates were 21.1% to 53.2% higher than non-inoculated medium. Under shaking culture condition, 90% to 95% of procymidone was degraded after 21 days treatment. Parathion was degraded in the range of 60% to 100% by B71 and B59, respectively. Otherwise 70% of alachlor was degraded by the two isolated bacteria during same period. The pH was not significantly affected for degradation of pesticides. The bacterial strains, B59 and B71 was identified as Acinetobacter sp. and as Pseudomonas sp. based on morphological, biochemical and physiological characteristics, and identity and similarity of automatic identification system, Biolog and MIDI.