• 제목/요약/키워드: cell-cycle inhibition

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Enhanced Growth Inhibition by Combined Gene Transfer of p53 and $p16^{INK4a}$ in Adenoviral Vectors to Lung Cancer Cell Lines (폐암세포주에 대한 p53 및 $p16^{INK4a}$의 복합종양억제유전자요법의 효과)

  • Choi, Seung -Ho;Park, Kyung-Ho;Seol, Ja-Young;Yoo, Chul-Gyu;Lee, Choon-Taek;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.1
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    • pp.67-75
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    • 2001
  • Background : Two tumor suppressor genes, p53 and p16, which have different roles in controlling the cell cycle and inducing apoptosis, are frequently inactivated during carcinogenesis including lung cancer. Single tumor suppressor gene therapies using either with p53 or p16 have been studied extensively. However, there is a paucity of reports regarding a combined gene therapy using these two genes. Methods : The combined effect of p53 and p16 gene transfer by the adenoviral vector on the growth of lung cancer cell lines and its interactive mechanism was investigated. Results : An isobologram showed that the co-transduction of p53 and p16 exhibited a synergistic growth in hibitory effect on NCI H358 and an additive effect on NCI H23. Cell cycle analysis demonstrated the induction of a synergistic G1/S arrest by a combined p53 and p16 transfer. This synergistic interaction was again confirmed in a soft agar confirmed in a soft agar clonogenic assay. Conclusion : These observations suggest the potential of a p53 and p16 combination gene therapy as another potent strategy in cancer gene therapy.

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Inhibition of Apoptosis by Nitric Oxide in MCF-7 Cells (유방암 세포(MCF-7)에서 nitric oxide에 의한 apoptosis 억제)

  • Kim, Kyun-Ha;Roh, Sang-Geun;Park, Hae-Ryun;Choi, Won-Chul
    • Journal of Life Science
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    • v.19 no.2
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    • pp.157-162
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    • 2009
  • Nitric oxide (NO) is a diffusible, multifunctional and transcellular messenger that has been implicated in numerous physiological and pathological conditions. It has been reported that NO induced apoptosis in tumor cells, macrophage cells and inhibited apoptosis in normal cells, endothelial cells. To examine whether NO could induce apoptosis in MCF-7 cells, cells were treated with SIN-1 (3-morpholinosydnonimine), NO donor. Cell viability did not change in SIN-1 treated cells for 48 h and there was no significantly changes in cell cycle progression or growth pattern by FACS analysis. But p53 protein, an apoptosis-related factor, increased SIN-1 treatment time dependently. Bcl-2, MDM2 and p21 were also accumulated. Bax level did not change. A major role of inhibiting apoptosis by NO in MCF-7 cells, cobalt chloride ($CoCl_2$) was added to cells preincubated with SIN-1. Whereas $CoCl_2$ treated cells underwent apoptosis, for 24 h SIN-1 preincubated cells were not induced apoptosis. Inactivated proteins, MDM2 and bcl-2, by $CoCl_2$ levels also increased in SIN-1 pre-treated cells. These results suggested that SIN-1 blocked p53 by MDM2 activation and inhibited apoptosis by inducing p21 and bcl-2 expression.

The Uptake of Lead Ion with Staphylococcus epidermidis (Staphylococcus epidermidis 를 이용한 납 이온의 축적에 관한 연구)

  • 김종혜;김말남
    • Korean Journal of Microbiology
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    • v.30 no.4
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    • pp.310-315
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    • 1992
  • Absorption of $\textrm{Pb}^{2-}$ from aqueous solution was studied using Staphylococcus epidermidis. Cells of exponential phase were employed as absorbents. Uptake ratio defined as the ratio of amount of $\textrm{Pb}^{2+}$ absorbed to that of initial $\textrm{Pb}^{2+}$. Absorption of $\textrm{Pb}^{2+}$ increased with increase in cell concentration. while amount of $\textrm{Pb}^{2+}$ per unit cell mass decreased. Uptake ratio of $\textrm{Pb}^{2+}$ augmented and then diminished after exhibiting a maximum as the pH of the solution increased. Equilibrium absorption of $\textrm{Pb}^{2+}$ deviated from Freundlich isotherm especially at higher concentration of $\textrm{Pb}^{2+}$ due to the precipitation phenomena. HCI and EDTA were founded to desorb $\textrm{Pb}^{2+}$ more effectively than $\textrm{Na}_{2}\textrm{CO}_{3}$ or $\textrm{NaHCO}_{3}$. After 10 cycles of absorption and desorption. $\textrm{Pb}^{2+}$ absorption capability remained almost unchanged and the biomass had leaked out 30-40 wt/%. Uptake ratio of Pb2+ decreased in the presence of other heavy metal ions due to the competitive absorption The inhibition of $\textrm{Pb}^{2+}$ absorption appeared to have a strong correlation with ionic radius of the competing ions. Especially $\textrm{Cr}^{3-}$, $\textrm{Co}^{2+}$ or $\textrm{Fe}^{2+}$ having smaller ionic radius depressed more significantly the uptake of $\textrm{Pb}^{2+}$ than any other metal ions tested.

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The Antitumor Effects of Selenium Compound $Na_5SeV_5O_{18}{\cdot}3H_2O$ in K562 Cell

  • Yang, Jun-Ying;Wang, Zi-Ren
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.859-865
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    • 2006
  • With an approach to study the anti-tumor effects and mechanism of selenium compound, we investigated the anti-tumor activity and mechanism of $Na_5SeV_5O_{18}{\cdot}3H_2O$ (NaSeVO) in K562 cells. The results showed that $0.625{\sim}20\;mg/L$ NaSeVO could significantly inhibit the proliferation of K562 cells in vitro in a time- and concentration-dependent manner as determined by microculture tetrazolium (MTT) assay, the IC50 values were 14.41 (4.45-46.60) and 3.45 (2.29-5.22) mg/L after 48 hand 72 h treatment with NaSeVO respectively. In vivo experiments demonstrated that i.p. administration of 5, 10 mg/kg NaSeVO exhibited an significant inhibitory effect on the growth of transplantation tumor sarcoma 180 (S180) and hepatoma 22 (H22) in mice, with inhibition rate 26.8% and 58.4% on S180 and 31.3% and 47.4% on H22, respectively. Cell cycle studies indicated that the proportion of G0/G1 phase was increased at 2.5 mg/L while decreased at 10 mg/L after treatment for 24, 48 h. Whereas S phase was decreased at 2.5-5 mg/L and markedly increased at 10 mg/L after treatment for 48 h. After treatment for 24 h, 10 mg/L NaSeVO also markedly increased S and G2/M phases. Take together, the result clearly showed that NaSeVO markedly increased S and G2/M phases at 10 mg/L. The study of immunocytochemistry showed that the expression bcl-2 is significantly inhibited by 10 mg/L NaSeVO, and bax increased. Morphology observation also revealed typical apoptotic features. NaSeVO also significantly caused the accumulation of $Ca^{2+}$ and $Mg^{2+}$, reactive oxygen species (ROS) and the reduction of pH value and mitochondrial membrane potential in K562 cells as compared with control by confocal laser scanning microscope. These results suggest that NaSeVO has anti-tumor effects and its mechanism is attributed partially to apoptosis induced by the elevation of intracellular $Ca^{2+}$, $Mg^{2+}$ and ROS concentration, and a reduction of pH value and mitochondria membrane potential (MMP).

Increased Apoptotic Efficacy of Decitabine in Combination with an NF-kappaB Inhibitor in Human Gastric Cancer AGS Cells (핵산합성 억제제인 decitabine과 NF-κB 활성 저해제인 PDTC의 병용 처리에 의한 인체 위암세포사멸 효과 증진)

  • Choe, Won Kyung;Choi, Yung Hyun
    • Journal of Life Science
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    • v.28 no.11
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    • pp.1268-1276
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    • 2018
  • The cytidine analog decitabine (DEC) acts as a nucleic acid synthesis inhibitor, whereas ammonium pyrrolidine dithiocarbamate (PDTC) is an inhibitor of nuclear factor-${\kappa}B$. The aim of this study was to investigate the possible synergistic inhibitory effect of these two inhibitors on proliferation of human gastric cancer AGS cells. The inhibitory effect of PDTC on AGS cell proliferation was significantly increased by DEC in a concentration-dependent manner, and this inhibition was associated with cell cycle arrest at the G2/M phase and the induction of apoptosis. This induction of apoptosis by the co-treatment with PDTC and DEC was related to the induction of DNA damage, as assessed by H2AX phosphorylation. Further studies demonstrated that co-treatment with PDTC and DEC induced the disruption of mitochondrial membrane potential, increased the generation of intracellular reactive oxygen species (ROS) and the expression of pro-apoptotic Bax, and down-regulated the expression of anti-apoptotic Bcl-2, ultimately resulting in the release of cytochrome c from the mitochondria into the cytoplasm. Co-treatment with PDTC and DEC also activated caspase-8 and caspase-9, which are representative caspases of the extrinsic and intrinsic apoptosis pathways. Co-treatment also activated caspase-3, which was accompanied by proteolytic degradation of poly (ADP-ribose) polymerase. Taken together, these data clearly indicated that co-treatment with PDTC and DEC suppressed the proliferation of AGS cells by increasing DNA damage and activating the ROS-mediated extrinsic and intrinsic apoptosis pathways.

Growth Inhibition against Contaminants in Aseptic Chocolate Milk Using Physicochemical Methods (물리.화학적 처리에 의한 멸균 초콜릿 우유 오염균의 생육억제 효과)

  • Choi, Moon-Kyoung;Yoon, So-Young;Lee, So-Young;Kim, Koth-Bong-Woo-Ri;Lee, Chung-Jo;Jung, Ji-Yeon;Kwak, Ji-Hee;Kim, Min-Ji;Kim, Dong-Hyun;SunWoo, Chan;Lee, Ju-Woon;Byun, Myung-Woo;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.8
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    • pp.1157-1163
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    • 2011
  • This study was conducted to investigate the cause of microbiological contaminants in aseptic chocolate milk and evaluate the effect of a physicochemical treatment on the growth inhibition of isolated bacterial strains. The bacterium isolated from aseptic chocolate milk was identified as Bacillus lentus and was named B. lentus M1. In the heat and pH treatment, the growth of B. lentus was inhibited at 110$^{\circ}C$ for >15 min and at pH's <5 and >10. An electrolyzed water treatment against B. lentus M1, revealed 5 mm growth past the inhibition zone. The effect of ozone gas on B. lentus M1 growth was evaluated using viable cell counts. When the initial number of B. lentus M1 was $10^2$ and $10^3$ CFU, the bacteria were completely suppressed by ozone gas treatment for 10 and 30 min, respectively. In a microwave treatment, B. lentus M1 was sterilized following microwave treatment for 1 min. As the result of ${\gamma}$-irradiation against B. lentus M1, numbers decreased as the ${\gamma}$-irradiation dosage increased. These results show the growth inhibition effects against contaminants in aseptic chocolate milk using physicochemical treatments.

Effects of Baicalin on Gene Expression Profiles during Adipogenesis of 3T3-L1 Cells (3T3-L1 세포의 지방세포형성과정에서 Baicalin에 의한 유전자 발현 프로파일 분석)

  • Lee, Hae-Yong;Kang, Ryun-Hwa;Chung, Sang-In;Cho, Soo-Hyun;Yoon, Yoo-Sik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.1
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    • pp.54-63
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    • 2010
  • Baicalin, a flavonoid, was shown to have diverse effects such as anti-inflammatory, anti-cancer, anti-viral, anti-bacterial and others. Recently, we found that the baicalin inhibits adipogenesis through the modulations of anti-adipogenic and pro-adipogenic factors of the adipogenesis pathway. In the present study, we further characterized the molecular mechanism of the anti-adipogenic effect of baicalin using microarray technology. Microarray analyses were conducted to analyze the gene expression profiles during the differentiation time course (0 day, 2 day, 4 day and 7 day) in 3T3-L1 cells with or without baicalin treatment. We identified a total of 3972 genes of which expressions were changed more than 2 fold. These 3972 genes were further analyzed using hierarchical clustering analysis, resulting in 20 clusters. Four clusters among 20 showed clearly up-regulated expression patterns (cluster 8 and cluster 10) or clearly down-regulated expression patterns (cluster 12 and cluster 14) by baicalin treatment for over-all differentiation period. The cluster 8 and cluster 10 included many genes which enhance cell proliferation or inhibit adipogenesis. On the other hand, the cluster 12 and cluster 14 included many genes which are related with proliferation inhibition, cell cycle arrest, cell growth suppression or adipogenesis induction. In conclusion, these data provide detailed information on the molecular mechanism of baicalin-induced inhibition of adipogenesis.

Transcriptome Analyses for the Anti-Adipogenic Mechanism of an Herbal Composition (생약복합물의 지방세포형성억제 기전규명을 위한 전사체 분석)

  • Lee, Hae-Yong;Kang, Ryun-Hwa;Bae, Sung-Min;Chae, Soo-Ahn;Lee, Jung-Ju;Oh, Dong-Jin;Park, Suk-Won;Cho, Soo-Hyun;Shim, Yae-Jie;Yoon, Yoo-Sik
    • Journal of Life Science
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    • v.20 no.7
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    • pp.1054-1065
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    • 2010
  • SH21B is a natural composition composed of seven herbs: Scutellaria baicalensis Georgi, Prunus armeniaca Maxim, Ephedra sinica Stapf, Acorus gramineus Soland, Typha orientalis Presl, Polygala tenuifolia Willd and Nelumbo nucifera Gaertner (Ratio 3:3:3:3:3:2:2). In our previous study, we reported that SH21B inhibited adipogenesis and fat accumulation in 3T3-L1 cells through modulation of various regulators in the adipogenesis pathway. The aim of this study was to analyze the transcriptome profiles for the anti-adipogenic effects of SH21B in 3T3-L1 cells. Total RNAs from SH21B-treated 3T3-L1 cells were reverse-transcribed into cDNAs and hybridized to Affymetrix Mouse Gene 1.0 ST array. From microarray analyses, we identified 2,568 genes of which expressions were changed more than two-fold by SH21B, and the clustering analyses of these genes resulted in 9 clusters. Three clusters among the 9 showed down-regulation by SH21B (cluster 4, cluster 6 and cluster 9), and two clusters showed up-regulation by SH21B (cluster 7 and cluster 8) during the adipogenesis of 3T3-L1 cells. It was found that many genes related to cell proliferation and adipogenesis were included in these clusters. Clusters 4, 6 and 9 included genes which were related with adipogenesis induction and cell cycle arrest. Clusters 7 and 8 included genes related to cell proliferation as well as adipogenesis inhibition. These results suggest that the mechanisms of the anti-adipogenic effects of SH21B may be the modulation of genes involved in cell proliferation and adipogenesis.

Anti-adipogenic Activity of Cortex ulmi pumilae Extract in 3T3-L1 Preadipocytes (유근피 추출물의 3T3-L1지방전구세포의 분화 억제 효능에 관한 연구)

  • Jeong, Hyun Young;Jin, Soojung;Nam, Soo Wan;Hyun, Sook Kyung;Kim, Sung Gu;Kim, Byung Woo;Kwon, Hyun Ju
    • Journal of Life Science
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    • v.24 no.2
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    • pp.137-147
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    • 2014
  • Cortex ulmi pumilae, the cortex of Ulmus davidiana var. japonica, has been used in traditional folk medicine for its anti-inflammatory effect. Although its various bioactivities such as anti-inflammatory, anti-microbial, and anti-cancer, have been reported, the anti-adipogenic activity of cortex ulmi pumilae remains unclarified. In the present study, we investigated the effect of cortex ulmi pumilae extract on adipocyte differentiation in 3T3-L1 preadipocytes. Treatment with cortex ulmi pumilae extract significantly reduced the formation of lipid droplets and triglyceride content in a dose-dependent manner; this is associated with an inhibition of the adipogenic transcription factors, CCAAT/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$). In addition, cortex ulmi pumilae extract treatment during the early stage of adipogenesis showed more efficient anti-adipogenic activity than treatment during other stages of adipogenesis. Cortex ulmi pumilae extract also inhibited cell proliferation and induced G1 arrest of 3T3-L1 cells in the early stage of adipogenesis. This was associated with upregulated expression of Cdk inhibitor p21 and downregulated expression of cyclin E and phospho-Rb, indicating that cortex ulmi pumilae extract blocks mitotic clonal expansion by cell cycle regulation. Taken together, these results suggest that cortex ulmi pumilae extract possesses anti-adipogenic activity through the inhibition of adipocyte differentiation by blocking mitotic clonal expansion.

Temporal Transcriptome Analysis of SARS-CoV-2-Infected Lung and Spleen in Human ACE2-Transgenic Mice

  • Jung Ah, Kim;Sung-Hee, Kim;Jung Seon, Seo;Hyuna, Noh;Haengdueng, Jeong;Jiseon, Kim;Donghun, Jeon;Jeong Jin, Kim;Dain, On;Suhyeon, Yoon;Sang Gyu, Lee;Youn Woo, Lee;Hui Jeong, Jang;In Ho, Park;Jooyeon, Oh;Sang-Hyuk, Seok;Yu Jin, Lee;Seung-Min, Hong;Se-Hee, An;Joon-Yong, Bae;Jung-ah, Choi;Seo Yeon, Kim;Young Been, Kim;Ji-Yeon, Hwang;Hyo-Jung, Lee;Hong Bin, Kim;Dae Gwin, Jeong;Daesub, Song;Manki, Song;Man-Seong, Park;Kang-Seuk, Choi;Jun Won, Park;Jun-Won, Yun;Jeon-Soo, Shin;Ho-Young, Lee;Jun-Young, Seo;Ki Taek, Nam;Heon Yung, Gee;Je Kyung, Seong
    • Molecules and Cells
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    • v.45 no.12
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    • pp.896-910
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    • 2022
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.