• Title/Summary/Keyword: Rb2/p130

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Acetylation of Retinoblastoma Like Protein2 (Rb2/p130) in Tumor Tissues

  • Khan, Z.N.;Sabir, M.;Kayani, M.A.;Saeed, M.
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2255-2258
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    • 2013
  • The activity of Rb proteins is controlled by post-translational modifications, especially through phosphorylation. Acetylation of Rb2/p130 was reported recently in NIH3T3 cells but its physiological relevance in cell cycle control and tumorigenesis is still unknown. Efforts are underway to investigate possible interplay between Rb2/p130 phosphorylation and acetylation. Here we hypothesized that Rb2/p130 acetylation, like p53 acetylation, may play a role in development of the tumor phenotype. The proposed hypothesis regarding acetylation of Rb2/p130 in tumor VS normal cells was found to be true in our case study of 36 tumor samples. Statistical analysis of results suggest strong correlation among Rb2/p130 acetylation and cancer phenotype.

G1 Arrest of U937 Human Monocytic Leukemia Cells by Sodium Butyrate, an HDAC Inhibitor, Via Induction of Cdk Inhibitors and Down-regulation of pRB Phosphorylation (Cdk inhibitors의 발현 증가 및 pRB 인산화 저해에 의한 HDAC inhibitor인 sodium butyrate에 의한 인체백혈병세포의 G1 arrest유발)

  • Choi, Yung-Hyun
    • Journal of Life Science
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    • v.19 no.7
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    • pp.871-877
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    • 2009
  • We investigated the effects of sodium butyrate, a histone deacetylase inhibitor, on the cell cycle progression in human monocytic leukemia U937 cells. Exposure of U937 cells to sodium butyrate resulted in growth inhibition, G1 arrest of the cell cycle and induction of apoptosis in a dose-dependent manner as measured by MTT assay and flow cytometry analysis. The increase in G1 arrest was associated with the down-regulation in cyclin D1, E, A, cyclin-dependent kinase (Cdk) 4 and 6 expression, and up-regulation of Cdk inhibitors such as p21 and p27. Sodium butyrate treatment also inhibited the phosphorylation of retinoblastoma protein (pRB) and p130, however, the levels of transcription factors E2F-1 and E2F-4 were not markedly modulated. Furthermore, the down-regulation of phosphorylation of pRB and p130 by this compound was associated with enhanced binding of pRB and E2F-1, as well as p130 and E2F-4, respectively. Overall, the present results demonstrate a combined mechanism involving the inhibition of pRBjp130 phosphorylation and induction of Cdk inhibitors as targets for sodium butyrate that may explain some of its anti-cancer effects in U937 cells.

Induction of Cdk inhibitor p27 and Inhibition of pRB Phosphorylation by Insamsapye-tang Treatment in Human Lung Cancer A549 Cells (인체 폐암세포에서 인삼사폐탕에 의한 Cdk inhibitor p27의 발현 증가 및 pRB의 인산화 억제)

  • Lee Min Woo;Seo Chang Hun;Park Cheol;Lee Won Ho;Choi Yung Hyun;Park Dong Il
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.213-219
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    • 2003
  • We investigated the effects of Insamsapye-tang (ISSPT) water extract on the cell proliferation of human lung carcinoma A549 cells. ISSPT treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner. This anti-proliferative effect of A549 cells by ISSSPT treatment was associated with morphological changes such as membrane shrinking and cell rounding up. DNA flow cytometric histograms showed that population of G1 phase of the cell cycle was increased by ISSPT treatment in a concentration-dependent manner. ISSPT treatment induced the levels of tumor suppressor p53 protein and cyclin-dependent kinase (Cdk) inhibitor p27 without significant alteration of cyclins and Cdks expression. In addition, ISSPT treatment resulted in down-regulation of phosphorylated retinoblastoma protein (pRB). However, the levels of p130, the pRB family protein, and transcription factors. E2F-1 and E2F-4. were remained unchanged. The present results indicated that ISSPT-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis, and we suggest that ISSPT will be an effective therapeutic agent on human lung cancer.

Characteristics of Isotherm, Kinetic, and Thermodynamic Parameters for Reactive Blue 4 Dye Adsorption by Activated Carbon (활성탄에 의한 Reactive Blue 4 염료의 흡착에 대한 등온선, 동력학 및 열역학적 특성)

  • Lee, Jong-Jib
    • Clean Technology
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    • v.26 no.2
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    • pp.122-130
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    • 2020
  • The isotherm, kinetic, and thermodynamic parameters of reactive blue 4 adsorbed by activated carbon were investigated for activated carbon dose, pH, initial concentration, contact time, and temperature data. The adsorption of the RB 4 dye by activated carbon showed a concave shape in which the percentage of adsorption increased in both directions starting from pH 7. The isothermal adsorption data were applied to Langmuir, Freundlich, and Temkin isotherms. Both Freundlich and Langmuir isothermal adsorption models fit well. From determined Freundlich separation factor (1/n = 0.125 ~ 0.232) and Langmuir separation factor (RL = 1.53 ~ 1.59), adsorption of RB 4 by activated carbon could be employed as an effective treatment method. The constant related to the adsorption heat (BT = 2.147 ~ 2.562 J mol-1) of Temkin showed that this process was physical adsorption. From kinetic experiments, the adsorption process followed the pseudo second order model with good agreement. The results of the intraparticle diffusion model showed that the inclination of the first straight line representing the surface diffusion was smaller than that of the second straight line representing the intraparticle pore diffusion. Therefore, it was confirmed that intraparticle pore diffusion is the rate-controlling step. The negative Gibbs free energy change (ΔG = -3.262 ~ -7.581 kJ mol-1) and the positive enthalpy change (ΔH = 61.08 kJ mol-1) indicated the spontaneous and endothermic nature of the adsorption process, proving this process to be spontaneous and endothermic.

G1 Arrest of the Cell Cycle by Gomisin N, a Dibenzocyclooctadiene Lignan, Isolated from Schizandra chinensis Baill in Human Leukemia U937 Cells (오미자에서 분리된 dibenzocyclooctadiene lignan의 일종인 gomisin N에 의한 인체혈구암세포의 세포주기 G1 arrest 유발)

  • Park, Cheol;Hwang, Hye-Jin;Choi, Byung-Tae;Choi, Tae-Hyun;Kim, Byung-Woo;Choi, Young-Whan;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.20 no.7
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    • pp.977-982
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    • 2010
  • We investigated the anti-cancer effects of two dibenzocyclooctadiene lignans, gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in human promyelocytic U937 cells. Gomisin N, but not gomisin A, inhibited cell growth in a concentration-dependent manner, which was associated with the induction of G1 arrest of the cell cycle. G1 arrest induced by gomisin N was correlated with down-regulation of cyclin E, cyclin-dependent kinase (Cdk) 2 and Cdk4, and a concomitant up-regulation of Cdk inhibitors such as p16 (INK4A) and p21 (WAF1/CIP1). Furthermore, gomisin N inhibited phosphorylation of retinoblastoma protein (pRB) and p130, and expression of transcription factor E2Fs. The results indicated that growth inhibition by gomisin N is related to cell cycle arrest at G1 in U937 cells and these findings suggest that gomisin N may be a useful chemotherapeutic agent.

Hepatocyte Growth Factor-mediated Regulation of OCT4 in human Mesenchymal Stem Cells

  • Ji-Eun Oh;Jung-Yoon Yoo;Eun Ju Lee;Sung Ryul Yu
    • Biomedical Science Letters
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    • v.30 no.3
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    • pp.123-130
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    • 2024
  • Mesenchymal stem cells (MSCs) hold great promise as a source of stem cells for therapy, but several limitations remain. We previously proposed that human embryonic stem cell-derived MSCs (hE-MSCs) expressing higher hepatocyte growth factor (HGF) levels were better alternatives, exhibiting greater expandability in vitro and greater therapeutic capacity in vivo. In this study, we aimed to examine the regulation of OCT4 expression in stem cells and to elucidate its underlying mechanism of transcriptional regulation of OCT4. We detected higher expression of OCT4, a stemness-associated gene in hE-MSCs than in human bone marrow-derived MSCs (hBM-MSCs). To determine the underlying regulatory mechanism of OCT4 expression in human MSCs (hMSCs), ELISA was performed using cell culture supernatants of hMSCs. Unlike fibroblast growth factor 2 or vascular endothelial growth factor, HGF was strongly expressed in hE-MSCs, also HGF treatment significantly increased OCT4 expression in hBM-MSC. Moreover, senescence-associated heterochromatin foci were decreased in HGF-treated hBM-MSCs compared with those in the HGF non-treated group. HGF increased Rb phosphorylation, and we confirmed the increased binding of E2F1 to the OCT4 promoter region at -233 from the transcription start point in the presence of HGF. Taken together, these results suggest that HGF-mediated regulation of OCT4 via E2F1 can help enhance the lifespan of hBM-MSCs during in vitro expansion.

Studies of Ginseng on the Antistress Effects (인삼(人蔘)의 항(抗)스트레스작용(作用)에 관(關)한 연구(硏究))

  • Kim, Nak-Doo;Hahn, Byung-Hoon;Lee, Eun-Bang;Kong, Jae-Yang;Kim, Myoung-Hye;Jin, Chang-Bae
    • Korean Journal of Pharmacognosy
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    • v.10 no.2
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    • pp.61-67
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    • 1979
  • Two pure saponin components, Panax saponin C (protopanaxatriol derivative, ginsenoside Re) and Panax saponin E (protopanaxadiol derivative, ginsenoside $Rb_l$) were isolated from Panax ginseng root and their acute toxicities in mice and antistress effects in rats were investigated. Average lethal doses $(LD_{50})$ of ginsenoside Re were 130mg/kg (i.v.), more than 1,000mg/kg (i.p.) and more than 1,500mg/kg (s.c.), respectively. Average lethal dose of ginsenoside $Rb_{1}$ was 243mg/kg intravenously. Adrenal ascorbic acid and cholesterol contents were significantly decreased when normal rats were exposed to heat $(40^{\circ}C)$ for 30 min. The reduction of the adrenal ascorbic acid and cholesterol contents in rats was partially prevented when the rats received the ginseng saponins prior to exposure to heat stress and most pronounced effects were observed in rats received ginsenoside Re. However, it was found that administration of ginseng alone, without stress, did not significantly change the ascorbic acid and cholesterol contents in adrenal glands. Eosinophil counts in the blood of the rats were elevated when the rats were exposed to the heat stress, and the elevation of the eosinophil counts were prevented with the ginseng saponins under the stress, but the changes were all insignificant statistically.

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Improved antimicrobial effect of ginseng extract by heat transformation

  • Xue, Peng;Yao, Yang;Yang, Xiu-shi;Feng, Jia;Ren, Gui-xing
    • Journal of Ginseng Research
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    • v.41 no.2
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    • pp.180-187
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    • 2017
  • Background: The incidence of halitosis has a prevalence of 22-50% throughout the world and is generally caused by anaerobic oral microorganisms, such as Fusobacterium nucleatum, Clostridium perfringens, and Porphyromonas gingivalis. Previous investigations on the structure-activity relationships of ginsenosides have led to contrasting results. Particularly, the antibacterial activity of less polar ginsenosides against halitosis-related bacteria has not been reported. Methods: Crude saponins extracted from the Panax quinquefolius leaf-stem (AGS) were treated at $130^{\circ}C$ for 3 h to obtain heat-transformed saponins (HTS). Five ginsenoside-enriched fractions (HTS-1, HTS-2, HTS-3, HTS-4, and HTS-5) and less polar ginsenosides were separated by HP-20 resin absorption and HPLC, and the antimicrobial activity and mechanism were investigated. Results: HPLC with diode-array detection analysis revealed that heat treatment induced an extensive conversion of polar ginsenosides (-Rg1/Re, -Rc, -Rb2, and -Rd) to less polar compounds (-Rg2, -Rg3, -Rg6, -F4, -Rg5, and -Rk1). The antimicrobial assays showed that HTS, HTS-3, and HTS-4 were effective at inhibiting the growth of F. nucleatum, C. perfringens, and P. gingivalis. Ginsenosides-Rg5 showed the best antimicrobial activity against the three bacteria, with the lowest values of minimum inhibitory concentration and minimum bactericidal concentration. One major reason for this result is that less polar ginsenosides can more easily damage membrane integrity. Conclusion: The results indicated that the less polar ginsenoside-enriched fraction from heat transformation can be used as an antibacterial agent to control halitosis.

Enzymatic Properties of the Convertible Enzyme of Ginseng Saponin Produced from Rhizopus japonicus (Rhizopus japonicus가 생산하는 인삼 Saponin 전환효소의 효소학적 특성)

  • 김상달;서정훈
    • Microbiology and Biotechnology Letters
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    • v.17 no.2
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    • pp.126-130
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    • 1989
  • In 14 kinds of ginsenosides in ginseng saponin, ginsenoside Rbr is contained the most abundantly. But ginsenoside Rd which is similar to ginsenoside R $b_1$in structure, was known to be superior to ginsenoside R $b_1$pharmaceutically. The convertible enzyme which can transform ginsenoside R $b_1$to Binsenoside Rd specifically among ginseng saponin, was purified homogeneously from Rhizopus japonicus. The optimal pH for the action of the enzyme was pH 4.8 to 5.0, and optimal temperature was 45$^{\circ}C$. The enzyme was stable in the range of pH 4.0 to 9.0, and the half activity of enzyme was remained by the thermal treatment at 6$0^{\circ}C$ for 2 hours. The enzyme activity was enhanced by addition of M $n^{++}$ or Fe, though inhibited by EDTA or o-phenanthroline. On the substrate specificity, the enzyme was. able to hydrolyze gentiobiose, cellobiose, amygdalin and prunasin, but not to hydrolyze any other kinds of Binsenosides besides Binsenoside R $b_1$. Km values of the enzyme for ginsenoside R $b_1$, gentiobiose and amygdalin were 5.0mM, 4.8mM and 3.7mM, respectively.3.7mM, respectively.y.

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