• Title/Summary/Keyword: cell cycle control

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Synergistic Effects of Exemestane and Aspirin on MCF-7 Human Breast Cancer Cells

  • Hu, Li-Xia;Du, Ying-Ying;Zhang, Ying;Pan, Yue-Yin
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5903-5908
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    • 2012
  • Objective: The purpose of this study is to investigate the combined effects of exemestane and aspirin on MCF-7 human breast cancer cells. Methods: Antiproliferative effects of exemestane and aspirin, alone and in combination, on growth of MCF-7 human breast cancer cells were assessed using the MTT assay. Synergistic interaction between the two drugs was evaluated in vitro using the combination index (CI) method. The cell cycle distribution was analyzed by flow cytometry and Western blotting was used to investigate the expression of cyclooxygenase-1, cyclooxygenase-2 and Bcl-2. Results: MTT assays indicated that combination treatment obviously decreased the viability of MCF-7 human breast cancer cells compared to individual drug treatment (CI<1). In addition, the combination of exemestane and aspirin exhibited a synergistic inhibition of cell proliferation, significantly arrested the cell cycle in the $G_0/G_1$ phase and produced a stronger inhibitory effect on COX-1 and Bcl-2 expression than control or individual drug treatment. Conclusion: These results indicate that the combination of exemestane and aspirin might become a useful method to the treatment of hormone-dependent breast cancer. The combination of the two inhibitors significantly increased the response as compared to single agent treatment, suggesting that combination treatment could become a highly effective approach for breast cancer.

Biological Effects of Smoking-induced Environmental Toxicity

  • Sohn, Sung-Hwa;Kim, In-Kyoung;Kim, Ki-Nam;Kim, Hye-Won;Seo, Sang-Hui;Lee, Seung-Ho;Kim, Yu-Ri;Lee, Eun-Il;Kim, Meyoung-Kon
    • Molecular & Cellular Toxicology
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    • v.2 no.3
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    • pp.202-211
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    • 2006
  • Our objective is to identify molecular factors which contribute to the increased risk of smoke in human. About 677 workers who had control and experimental groups according to their urinary Naphthol levels were enrolled in our study. In the present study, we investigated the effects of smoking on gene expression profiles in human. We determined differential gene expression patterns in smoker versus non-smoker using cDNA microarray. Specific genes were up-or down-regulated according to smoking and age. Inflammatory related genes such as cytokine, interleukin, and tumor necrosis factor were up-regulated, DNA repair related genes such as high-mobility group (nonhistone chromosomal) protein 1, and protein 2 were down-regulated, apoptosis related genes such as myeloperoxidase and Bcl-2-associated athanogene were down-regulated, and cell cycle related genes were down-regulated. In our epidemiological study, notably, inflammatory, DNA repair, apoptosis, signal transduction, metabolism, cell cycle, cell proliferation, transcription related genes were regulated.

Computational approaches for prediction of protein-protein interaction between Foot-and-mouth disease virus and Sus scrofa based on RNA-Seq

  • Park, Tamina;Kang, Myung-gyun;Nah, Jinju;Ryoo, Soyoon;Wee, Sunghwan;Baek, Seung-hwa;Ku, Bokkyung;Oh, Yeonsu;Cho, Ho-seong;Park, Daeui
    • Korean Journal of Veterinary Service
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    • v.42 no.2
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    • pp.73-83
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    • 2019
  • Foot-and-Mouth Disease (FMD) is a highly contagious trans-boundary viral disease caused by FMD virus, which causes huge economic losses. FMDV infects cloven hoofed (two-toed) mammals such as cattle, sheep, goats, pigs and various wildlife species. To control the FMDV, it is necessary to understand the life cycle and the pathogenesis of FMDV in host. Especially, the protein-protein interaction between FMDV and host will help to understand the survival cycle of viruses in host cell and establish new therapeutic strategies. However, the computational approach for protein-protein interaction between FMDV and pig hosts have not been applied to studies of the onset mechanism of FMDV. In the present work, we have performed the prediction of the pig's proteins which interact with FMDV based on RNA-Seq data, protein sequence, and structure information. After identifying the virus-host interaction, we looked for meaningful pathways and anticipated changes in the host caused by infection with FMDV. A total of 78 proteins of pig were predicted as interacting with FMDV. The 156 interactions include 94 interactions predicted by sequence-based method and the 62 interactions predicted by structure-based method using domain information. The protein interaction network contained integrin as well as STYK1, VTCN1, IDO1, CDH3, SLA-DQB1, FER, and FGFR2 which were related to the up-regulation of inflammation and the down-regulation of cell adhesion and host defense systems such as macrophage and leukocytes. These results provide clues to the knowledge and mechanism of how FMDV affects the host cell.

Effects of intrauterine growth restriction during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses

  • Zi, Yang;Ma, Chi;He, Shan;Yang, Huan;Zhang, Min;Gao, Feng;Liu, Yingchun
    • Animal Bioscience
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    • v.35 no.7
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    • pp.989-998
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    • 2022
  • Objective: This study investigated the effects of intrauterine growth restriction (IUGR) during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses. Methods: Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/body weight [BW]0.75/d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW0.75/d, n = 6) and control group (CG, ad libitum, 0.67 MJ ME/BW0.75/d, n = 6). Fetuses were recovered at slaughter on d 140. Results: The G0/G1 phase cell number in fetal thymus of the RG1 group was increased but the proliferation index and the expression of proliferating cell nuclear antigen (PCNA) were reduced compared with the CG group (p<0.05). Fetuses in the RG1 group exhibited decreased growth hormone receptor (GHR), insulin-like growth factor 2 receptor (IGF-2R), and their mRNA expressions (p<0.05). For the RG2 fetuses, there were no differences in the proliferation index and PCNA expression (p>0.05), but growth hormone (GH) and the mRNA expression of GHR were lower than those of the CG group (p<0.05). The thymic mRNA expressions of cyclin-dependent protein kinases (CDKs including CDK1, CDK2, and CDK4), CCNE, E2-factors (E2F1, E2F2, and E2F5) were reduced in the RG1 and RG2 groups (p<0.05), and decreased mRNA expressions of E2F4, CCNA, CCNB, and CCND were occurred in the RG1 fetuses (p<0.05). The decreased E-cadherin (E-cad) as a marker for epithelial-mesenchymal transition (EMT) was found in the RG1 and RG2 groups (p<0.05), but the OB-cadherin which is a marker for activated fibroblasts was increased in fetal thymus of the RG1 group (p<0.05). Conclusion: These results indicate that weakened GH/IGF signaling system repressed the cell cycle progression in G0/G1 phase in IUGR fetal thymus, but the switch from reduced E-cad to increased OB-cadherin suggests that transdifferentiation process of EMT associated with fibrogenesis was strengthened. The impaired cell growth, retarded proliferation and modified differentiation were responsible for impaired maturation of IUGR fetal thymus.

Effects of Superovulation and Fertilization on Gonadotrophic Hormone Levels in the Golden Hamster (성선자극 Hormone 수준이 Golder Hamster의 과배란 및 수정에 미치는 영향)

  • 우제석;이규승;서길웅;박창식
    • Korean Journal of Animal Reproduction
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    • v.13 no.1
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    • pp.26-31
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    • 1989
  • This study was carried out to investigate the effects of PMSG and/or HCG treatment on superovulation and fertilization in the golden hamster. The results obtained were summarized as follows: 1. The female groups treated with 30 IU PMSG or 30 IU PMSG+25IU HCG ovulated more eggs than those treated with 15 IU PMSG or 15 IU PMSG+25IU HCG(P<.01). All the PMSG treatment groups superovulated as compared with the untreated control group(P<.01). There were no differences on fertilization rate between the superovulated groups and the control group. 2. The fertilized ova were obtained only by the female group treated with 30 IU PMSG at 1000hr on day 1(morning of ovulation) of the estrous cycle. 3. The intervals between PMSG and HCG injection necessary to obtain the consistent superovulation and fertilized ova were 66hr and 72hr. 4. The superovulated ova were collected from oviduct 48hr, oviduct and uterus 72hr, and uterus 96 hr after mating. 80.3% of two cell, 75.8% of eight cell, and 73.7% of blastocyst of the ovulated ova occurred 48hr, 72hr, and 96hr after mating, respectively.

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Effect of p16 on glucocorticoid response in a B-cell lymphoblast cell line

  • Kim, Sun-Young;Lee, Kyung-Yil;Jeong, Dae-Chul;Kim, Hak-Ki
    • Clinical and Experimental Pediatrics
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    • v.53 no.7
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    • pp.753-758
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    • 2010
  • Purpose: It has been suggested that p16 has a role in glucocorticoid (GC)-related apoptosis in leukemic cells, but the exact mechanisms have yet to be clarified. We evaluated the relationship between the GC response and p16 expression in a lymphoma cell line. Methods: We used p16 siRNA transfection to construct p16-inactivated cells by using the B-cell lymphoblast cell line NC-37. We compared glucocorticoid receptor (GR) expression, apoptosis, and cell viability between control (p16+NC-37) and p16 siRNA-transfected (p16-NC-37) cells after a single dose of dexamethasone (DX). Results: In both groups, there was a significant increase in cytoplasmic GR expression, which tended to be higher for p16+NC-37 cells than for p16- NC37 cells at all times, and the difference at 18 h was significant (P<0.05). Similar patterns of early apoptosis were observed in both groups, and late apoptosis occurred at higher levels at 18 h when the GR had already been downregulated ($P$<0.05). Cell viability decreased in both groups but the degree of reduction was more severe in p16+NC-37 cells after 18 h ($P$<0.05). Conclusion: These results suggest a relationship between GR expression and cell cycle inhibition, in which the absence of p16 leads to reduced cell sensitivity to DX.

The effect of Sparganii Rhizoma on the proliferation inhibition of human uterine leiomyoma cell and expression of gene related cell apoptosis (삼릉(三稜)이 자궁근종세포의 증식억제와 세포자멸사 관련 발현에 미치는 영향)

  • Park, Chang-Gun;Baek, Seung-Hee;Kim, Dong-Chul
    • The Journal of Korean Obstetrics and Gynecology
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    • v.19 no.2
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    • pp.199-213
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    • 2006
  • Purpose : This study was aimed to investigate the inhibitory effect of Sparganii Rhizoma on the proliferation of human uterine leiomyoma cells and the expression of gene related the mechanism of cell apoptosis. Methods : This study was evaluated the number of death cells treated with indicated concentration of Sparganii Rhizoma and investigated cell death rate by MTS assay. Furthermore, fluorescence-activated cell sorter analysis and DNA fragmentation assay were used to dissect between necrosis and apoptosis. and then we observed the differential gene expression by western blot analysis. Results :1) The inhibitory effect on the growth of uterine leiomyoma cell treated with Sparganii Rhizoma was increased in a dose dependent manner. 2) As the result of FACS analysis, subG1 phase incrase was observed 23.49% inuterine leiomyoma cell treated with Sparganii Rhizoma at $500\;{\mu}g/ml$ compared to control.. 3) The gene expression of p53, p21 related cell apoptosis was increased according to increasing concentration but p27 was none exchanged. 4) The expression of cyclin A, D and E was decreased in a concentration proportional and then the dephosphorylation of pRb was increased. 5) The character of apoptosis, DNA fragmentation was significantly observed according to increasing concentration. 6) The expression of pro-caspase3 were decreased dependent on treatment concentration and activated PARP took place. Conclusion : The inhibitory effect of Sparganii Rhizoma on the proliferation of human uterine leiomyoma cells was observed with apoptosis and cell cycle arrest. These data suggest that Sparganii Rhizoma might be candidate of medical therapy for uterine leiomyoma.

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Regulation of Cyclin D3 by Calpain Protease in Human Breast Carcinoma MDA-MB-231 Cells (인체 유방암세포에서 calpain protease에 의한 cyclin D3의 발현 조절)

  • Choi, Byung-Tae;Kim, Gun-Do;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.16 no.4
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    • pp.598-604
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    • 2006
  • The $Ca^{2+}-activated$ neutral protease calpain induced proteolysis has been suggested to play a role in certain cell growth regulatory proteins. Cyclin proteolysis is essential for cell cycle progression. D-type cyclins, which form an assembly with cyclin-dependent kinases (cdk4 and cdk6), are synthesized earlier in G1 of the cell cycle and seem to be induced in response to external signals that promote entry into the cell cycle. Here we show that cyclin D3 protein levels are regulated at the posttranscriptional level by calpain protease. Treatment of human breast carcinoma MDA-MB-231 cells with lovastatin and actinomycin D resulted in a loss of cyclin D3 protein that was completely reversible by the peptide aldehyde calpain inhibitor, LLnL. The specific inhibitor of the 26S proteasome, lactacystin, the lysosome inhibitors, ammonium chloride and chloroquine, and the serine protease inhibitor, phenylmethylsulfonylfluoride (PMSF), did not block the degradation of cyclin D3 by lovastatin and actinomycin D. Results of in vitro degradation of cyclin D3 by purified calpain showed that cyclin D3 protein is degraded in a $Ca^{2+}-dependent$ manner, and the half-life of cyclin D3 protein was dramatically increased in LLnL treated cells. These data suggested that cyclin D3 protein is regulated by the $Ca^{2+}-activated$ protease calpain.

A PDPWM Based DC Capacitor Voltage Control Method for Modular Multilevel Converters

  • Du, Sixing;Liu, Jinjun;Liu, Teng
    • Journal of Power Electronics
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    • v.15 no.3
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    • pp.660-669
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    • 2015
  • This paper presents a control scheme with a focus on the combination of phase disposition pulse width modulation (PDPWM) and DC capacitor voltage control for a chopper-cell based modular multilevel converter (MMC) for the purpose of eliminating the time-consuming voltage sorting algorithm and complex voltage balancing regulators. In this paper, the convergence of the DC capacitor voltages within one arm is realized by charging the minimum voltage module and discharging the maximum voltage module during each switching cycle with the assistances of MAX/MIN capacitor voltage detection and PDPWM signals exchanging. The process of voltage balancing control introduces no extra switching commutation, which is helpful in reducing power loss and improving system efficiency. Additionally, the proposed control scheme also possess the merit of a simple executing procedure in application. Simulation and experimental results indicates that the MMC circuit together with the proposed method functions very well in balancing the DC capacitor voltage and improving system efficiency even under transient states.

Study on the Change of Physical and Anatomical Properties in the Pine Wood by Accelerated Weathering Test (촉진열화실험에 의한 소나무의 물성 및 조직 변화에 대한 연구)

  • Kim, Gwang-Chul
    • Journal of the Korea Furniture Society
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    • v.23 no.3
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    • pp.324-331
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    • 2012
  • The domestic pine was used to investigate the change of specific gravity, moisture contents, color and anatomical structure by accelerated weathering test (AWT). According to visual inspection, a few knot separation and looseness as well as considerable surface discoloration was found out. However, the crack and split of surface texture have been never occurred till the last step of AWT. On the whole, as the time of accelerated weathering test has increased, the specific gravity has decreased. Finally, after the 9th week of AWT, the specific gravity was 0.38 that reached to 82% compared to the control specimen. In case of moisture content (MC), it showed rising trend in its early stages, however, after 3th week of AWT it have displayed steady state. A deterioration of cell-wall components was not remarkably observed by scanning electron microscope (SEM), however the ray fractures of AWT specimen were observed more than those of control specimen. The full fracture of epithelial cell around resin canal was observed by optical microscope. The fracture of ray of 2th cycle AWT specimen was first, followed by 1th week and control group. A distortion of tracheid for early spring wood and fracture of epithelial cell were generally observed by a similar level, regardless of duration time of AWT. Therefore, it is obvious that increasing duration time of AWT does not affect the deterioration of micro-structure for wood members from this study. Although a considerable change of anatomical properties was not found, there is a need of further research to understand how will the changes of specific gravity and MC on the physical properties of wood member.

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