• Title/Summary/Keyword: p53-independent p21

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Suppression of Human Prostate Cancer Cell Growth by β-Lapachone via Down-regulation of pRB Phosphorylation and Induction of Cdk Inhibitor p21WAF1/CIP1

  • Choi, Yung-Hyun;Kang, Ho-Sung;Yoo, Mi-Ae
    • BMB Reports
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    • v.36 no.2
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    • pp.223-229
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    • 2003
  • The product of a tree (Tabebuia avellanedae) from South America, $\beta$-lapachone, is known to exhibit various pharmacological properties, the mechanisms of which are poorly understood. The aim of the present study was to further elucidate the possible mechanisms by which $\beta$-lapachone exerts its anti-proliferative action in cultured human prostate cancer cells. We observed that the proliferation-inhibitory effect of $\beta$-lapachone was due to the induction of apoptosis, which was confirmed by observing the morphological changes and cleavage of the poly(ADP-ribose) polymerase protein. A DNA flow cytometric analysis also revealed that $\beta$-lapachone arrested the cell cycle progression at the G1 phase. The effects were associated with the down-regulation of the phosphorylation of the retinoblastoma protein (pRB) as well as the enhanced binding of pRB and the transcription factor E2F-1. Also, $\beta$-lapachone suppressed the cyclindependent kinases (Cdks) and cyclin E-associated kinase activity without changing their expressions. Furthermore, this compound induced the levels of the Cdk inhibitor $p21^{WAF1/CIP1}$ expression in a p53-independent manner, and the p21 proteins that were induced by $\beta$-lapachone were associated with Cdk2. $\beta$-lapachone also activated the reporter construct of a p21 promoter. Overall, our results demonstrate a combined mechanism that involves the inhibition of pRB phosphorylation and induction of p21 as targets for $\beta$-lapachone. This may explain some of its anticancer effects.

G1 Arrest of the Cell Cycle by Onchungeum in Human Hepatocarcinoma Cells (온청음(溫淸飮)이 인체 간암세포의 세포주기 G1 Arrest에 미치는 영향)

  • Goo, In-Moo;Shin, Heung-Mook
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.4
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    • pp.821-828
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    • 2008
  • Onchungeum, a herbal formula, which has been used for treatment of anemia due to bleeding, discharging blood and skin disease. In the present study, it was examined the effects of extract of Onchungeum (OCE) on the growth of human hepatocarcinoma cell lines Hep3B (p53 null type) and HepG2 (p53 wild type) in order to investigate the anti-proliferative mechanism by OCE. Treatment of Hep3B and HepG2 cells to OCE resulted in the growth inhibition in a dose-dependent manner, however Hep3B cell line exhibited a relatively strong anti-proliferative activity to OEC. Flow cytometric analysis revealed that OCE treatment in Hep3B cells caused G1 phase arrest of the cell cycle, which was associated with various morphological changes in a dose-dependent fashion. RT-PCR and immunoblotting data revealed that treatment of OCE caused the down-regulation of cyclin D1 expression, however the levels of cyclin E expression were not changed by OCE. The G1 arrest of the cell cycle was also associated with the induction of Cdk inhibitor p27 by OCE. Because the p53 gene is null in Hep3B cells, it is most likely that the induction of p21 is mediated through a p53-independent pathway. Moreover, p27 detected in anti-Cdk4 and anti-Cdk2 immunoprecipitates from the OCE-treated cells, suggesting that OCE-induced p27 protein blocks Cdk kinase activities by directing binding to the cyclin/Cdk complexes. Furthermore, OCE treatment potently suppresses the phosphorylation of retinoblastoma proteins and the levels of the transcription factor E2F-1 expression. Taken together, these results indicated that the growth inhibitory effect of OCE in Hep3B hepatoma cells was associated with the induction of G1 arrest of the cell cycle through regulation of several major growth regulatory gene products.

Induction of G2/M Arrest of the Cell Cycle by Genistein in Human Bladder Carcinoma and Leukemic Cells (인체 방광암 및 백혈병세포에서 genistein에 의한 세포주기 G2/M arrest 유발에 관한 연구)

  • Kim, Eu-Kyum;Myong, You-Ho;Song, Kwan-Sung;Lee, Ki-Hong;Rhu, Chung-Ho;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.16 no.4
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    • pp.589-597
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    • 2006
  • Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and DNA topoisomerase activities. There are several studies documenting molecular alterations leading to cell cycle arrest and induction of apoptosis by genistein as a chemopreventive agent in a variety of cancer cell lines; however, its mechanism of action and its molecular targets on human bladder carcinoma and leukemic cells remain unclear. In the present study, we have addressed the mechanism of action by which genistein suppressed the proliferation of T24 bladder carcinoma and U937 leukemic cells. Genistein significantly inhibited the cell growth and induced morphological changes, and induced the G2/M arrest of the cell cycle in both T24 and U937 cells with a relatively stronger cytotoxicity in U937. The G2/M arrest in T24 cells was associated with the inhibition of cyclin A, cyclin B1 and Cdc25C protein expression without alteration of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1). However, the inhibitory effects of genistein on the cell growth of U937 cells were connected with a marked inhibition of cyclin B1 and an induction of Cdk inhibitor p21 proteins by p53-independent manner. These data suggest that genistein may exert a strong anticancer effect and additional studies will be needed to evaluate the different mechanisms between T24 and U937 cells.

Clinical Characteristics and Prognosis of Gastrointestinal Stromal Tumors of Stomach (위의 위장관 간질 종양의 임상적 특징 및 예후)

  • Kim, Min-Hyung;Hur, Hoon;Kim, Sin-Sun;Kim, Sung-Keun;Jeon, Kyung-Hwa;Song, Kyo-Young;Kim, Jin-Jo;Jin, Hyung-Min;Kim, Wook;Park, Cho-Hyun;Park, Seung-Man;Lim, Keun-Woo;Jeon, Hae-Myung
    • Journal of Gastric Cancer
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    • v.6 no.3
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    • pp.146-153
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    • 2006
  • Purpose: Gastrointestinal stromal tumorsm (GISTs) are the most common mesenchymal tumors that arise anywhere in the tubular GI tract. The prognosis for GSTIs is important because f GISTs may metastasiwx in the liver or the abdominal cavity in an early stage. For the reason we examined the tumor size, the mitotic number, ki 67, p53, and c-kit mutation as independent prognostic factor for GISTs. Materials and Methods: A retrospective study was conducted in 76 patients who had been re-evaluated for confirmation of diagnosis between Jan 1998 and Dec. 2001. at Catholic University of medicine. Results: There were significant difference between the turner size, mitotic indices, ki 67, c-kit mutations and the 5-years survival rates. Tumor size (${\geq}5\;cm$) and mitotic index (${\geq}5/50\;HPF$) were statistically related to a significantly poor prognosis (P=0.017 and P=0.042, respectively). c-kit mutations in exon 11 were found in 7 cases c-kit mutation was observed more frequently in high risk patients, and there was a significant difference between c-kit mutation and survival (P=0.037). Elevated ki 67 was noted in 34 out of the 76 cases. High risk patients showed elevated ki67 index more frequently and there was significant relation with the survival rate (P=0.0417). Conclusion: We think that tumor size, mitotic index, Ki 67 and c-kit mutation are as independent prognostic factors for GISTs, but more research is needed.

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Crocetin Induces Cytotoxicity in Colon Cancer Cells Via p53-independent Mechanisms

  • Li, Cai-Yan;Huang, Wen-Feng;Wang, Qun-Li;Wang, Fan;Cai, E.;Hu, Bing;Du, Jia-Cheng;Wang, Jing;Chen, Rong;Cai, Xiao-Jing;Feng, Jing;Li, Hui-Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3757-3761
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    • 2012
  • Objective: Crocin has been proposed as a promising candidate for cancer chemoprevention. The purpose of this investigation was to investigate the chemopreventive action and the possible mechanisms of crocin against human colon cancer cells in vitro. Methods: Cell proliferation was examined using MTT assay and the cell cycle distribution fractions were analyzed using fow cytometric analysis after propidium iodide staining. Apoptosis was detected using theTUNEL Apoptosis Detection Kit with laser scanning confocal microscope. DNA damage was assessed using the alkaline single-cell gel electrophoresis assay, while expression levels of p53, cdk2, cyclinA and P21 were examined by Western blot analysis. Results: Treatment of SW480 cells with crocetin (0.2, 0.4, 0.8 mmol/L) for 48 h signifcantly inhibited their proliferation in a concentration-dependent manner. Crocetin (0.8 mmol/L) signifcantly induced cell cycle arrest through p53-independent mechanisms accompanied by P21 induction. Crocetin (0.8 mmol/L) caused cytotoxicity in the SW480 cells by enhancing apoptosis and decreasing DNA repair capacity in a time-dependent manner. Conclusions: This report provides evidence that crocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug.

Penicillium Diversity from Intertidal Zone in Korea

  • Park, Myung Soo;Lee, Seobihn;Oh, Seung-Yoon;Lim, Young Woon
    • 한국균학회소식:학술대회논문집
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    • 2016.05a
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    • pp.11-11
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    • 2016
  • Penicillium species are commonly isolated from various outdoor and indoor environments, including marine environments such as sponges, algae and sand. Penicillium is especially important because numerous bioactive compounds have been isolated. Penicillium was the most common species in intertidal zone in Korea, however the diversity and ecological roles of Penicillium in intertidal zone are not clarified. We explored diversity and ecological roles of marine-derived Penicillium from tidal flat and sea sand in Korea. The diversity of marine-derived Penicillium from Korea was investigated using both culture-dependent and culture-independent approach by ${\beta}$-tubulin sequence. In addition, we evaluated optimal temperature, halo-tolerance, and enzyme activity of Penicillium strains, such as extracellular alginase, endoglucanase, ${\beta}$-glucosidase, and protease. For culture-dependent approach, a total of 182 strains of 62 Penicillium species were isolated, with 53 species being identified. The most common species was Penicillium oxalicum, followed by P. crustosum, P. brasilianum, P. koreense, and P. griseofulvum. Species richness and composition were not significantly different by season, substrates, and seaside. For culture-independent approach using Illumina sequencing, 73 OTUSs were detected. The most frequently observed species was P. antarcticum, followed by P. koreense, P. crustosum, and P. brevicompactum. Diversity of Penicillium was higher during winter season than during summer season and in western sea than in southern sea, respectively. Community structure was significantly different by season and sea side. 52 species were detected by both methods. Unique species were isolated from each of methods - 10 from culture methods and 21 from Illumina sequencing. Furthermore, salinity adaption of the Penicillium varied depending on species. Many Penicillium species showed endoglucanase, ${\beta}$-glucosidase, and protease activity. Some species including P. paneum and P. javanicum degraded the polycyclic aromatic hydrocarbons. Thus, our results demonstrate that intertidal zone in Korea harbors diverse Penicillium community and marine-derived Penicillium play important ecological roles as decomposers of organic material in marine environments.

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The Current State and Determinants of Korean Baby-Boomers' Welfare Consciousness

  • Lee, Hyoung-Ha
    • Journal of the Korea Society of Computer and Information
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    • v.21 no.5
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    • pp.193-200
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    • 2016
  • This study was conducted in order to assess the effect of variables influencing Korean baby-boomers' welfare consciousness. For this purpose, data from the $8^{th}$ supplementary survey of the Korea Welfare Panel in 2013 were analyzed. The subjects of analysis were 2,035 people who were born between 1955 and 1965 whose welfare panel data did not have missing values for the variables of the research model. According to the results of analysis, first, when the descriptive statistics of the major variables were analyzed, those showing a relatively high mean score among the sub-factors of the baby-boomers' welfare consciousness were 'expansion of expenditure for public assistance' (mean 3.65, SD .557), 'expansion of expenditure for social insurance' (mean 3.53, SD .646), and 'expansion of expenditure for social services' (mean 3.26, SD .424). The mean score of the baby-boomers' overall welfare consciousness was relatively high as 3.45 (SD .428), advocating the expansion of welfare expenditure. Second, the independent variables influencing the baby-boomers' welfare consciousness was found to have explanatory power of 12.9%. In the results of regression analysis, variables found to have a significant effect were gender (B=.100, t=2.573, p<.01), personal responsibility for poverty (B=-.151, t=-3.635, p<.01), social responsibility for poverty (B=.149, t=3.437, p<.001), and recipient's laziness (B=.251, t=6.578, p<.001). Based on these results were discussed major relevant policies.

The Study of Blood metabolic Variation on 10Km Horseback Riding and Running (10km 승마운동과 달리기 운동 시 혈중 대사 변화 연구)

  • Nam, Sang-Nam;Park, Jeong-Bum
    • Journal of the Korea Convergence Society
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    • v.9 no.4
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    • pp.381-386
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    • 2018
  • This study aims to provide a scientific proof of the effects of horseback riding sports by analyzing changes in metabolic variation of horseback riding and running before and after 10km running. Paired t-test and independent t-test were conducted to process the data. The results show that among lipid source glucose significantly increases for horseback riding group $97.78{\pm}14.55mg/dl$ to $123.21{\pm}33.88mg/dl$, (p<.05). TC horseback riding group $188.71{\pm}35.25mg/dl$ to $199.35{\pm}32.79mg/dl$(p<.01), LDL-C also significant increases in riding group $113.42{\pm}33.39mg/dl$ to $121.42{\pm}32.52mg/dl$(p<.01). HDL-C also shows significant increase; in riding group $53.42{\pm}14.36mg/dl$ to $56.64{\pm}15.24mg/dl$(p<.01). show that among lipid variation glucose significantly change in horseback riding group, TC horseback riding group, LDL-C also change in riding group.

The Effects of Empathy and Gender Role Identity on Communication Competence in Nursing College Students (간호대학생의 공감능력, 성역할 정체성이 의사소통능력에 미치는 영향)

  • Choi, Hyun Sook;Kim, Kyung Ae;Lee, SankBok;Joung, Hyeyoung
    • Journal of Korean Critical Care Nursing
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    • v.13 no.3
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    • pp.41-50
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    • 2020
  • Purpose : This descriptive research study aimed to identify the factors influencing nursing students' empathy and gender role identity and their effect on communication competence. Methods : Participants were 183 senior nursing students who had completed a clinical practice and simulation-based practical training course. Using the IBM SPSS/WIN 21.0 program, general characteristics were analyzed using descriptive statistics, independent variables were compared with t-tests and 𝑥2 tests, and influencing factors on each variable and communication underwent multiple linear regression analysis. Results : Communication competence showed significant correlations with empathy (r=.40, p<.001), gender role identity (r=.53, p<.001), major satisfaction (r=.18, p=.013), and peer relationships (r=.24, p<.001). When gender was entered as a covariate, empathy (t=4.41, p<.001) and gender role identity (t=6.97, p<.001) were identified as predictors affecting communication competence with 36% explanation power (R2=.36, p<.001). Conclusion : The findings of this study suggest that course subjects considering the gender identities of students should be developed through various programs to establish students' identity as nurses and improve their empathy and communication.

Mechanism of gemcitabine-induced apoptosis (Gemcitabine의 세포사멸 기전 연구)

  • Seol, Jae-Won;Lee, You-Jin;Kang, Dong-Won;Kang, Hyung-Sub;Kim, Nam-Soo;Kim, In-Shik;Park, Sang-Youel
    • Korean Journal of Veterinary Research
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    • v.45 no.4
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    • pp.495-500
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    • 2005
  • The nucleoside analogue gemcitabine (2', 2-difluorideoxycytide) is potential against a wide variety of solid tumors and considered to be one of the most active drugs in the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated the signals of gemcitabine-induced apoptosis, especially in point of caspase pathway in A549. We exposed A549 cells to gemcitabine for dose/time dependent manner and the results showed that gemcitabine induced apoptotic cell death in a time/dose-dependent manner. We also treated to gemcitabine and Z-VAD-fmk as a pan-caspase inhibitor for 24 hours. Gemcitabine alone induced 35.3% cell death, and co-treatment with gemcitabine and Z-VAD-fmk induced 15.1% apoptotic cell death. Our results demonstrated that Z-VAD-fmk as a pan-caspase did not completely block the gemcitabine-induced apoptosis. Western blotting analysis showed that gemcitabine increased caspase-3, active caspase-8, p21 and p53 protein expressions in A549. Co-treatment with Z-VAD-fmk completely blocked caspase-3 and active caspase-8 protein expressions, but did not change the level of p21 and p53 protein expressions. Our data indicate that gemcitabine induced apoptosis through caspase-dependent and -independent pathways in A549.