• Title/Summary/Keyword: Growth-inhibitor

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Role of Intracellular Calcium in Clotrimazole-Induced Alteration of Cell Cycle Inhibitors, p53 and p27, in HT29 Human Colon Adenocarcinoma Cells

  • Thapa, Dinesh;Kwon, Jun-Bum;Kim, Jung-Ae
    • Biomolecules & Therapeutics
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    • v.16 no.1
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    • pp.21-27
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    • 2008
  • Clotrimazole (CLT), a potent antifungal drug, is known to inhibit tumor cell proliferation. In the present study, we examined the role of intracellular $Ca^{2+}$ in CLT-induced cell cycle arrest of colon adenocarcinoma HT29 cells. CLT inhibited growth of HT29 cells in a concentration-dependent manner, which was associated with inhibition of cell cycle progression at the G(1)-S phase transition and an increase in the expression of cell cycle inhibitor proteins p27 and p53. CLT also suppressed the $Ca^{2+}$ overload by A23187, a calcium ionophore, suggesting its role in modulation of intracellular $Ca^{2+}$ concentration in HT29 cells. The simultaneous application of CLT and A23187 with addition of $CaCl_2$ (1mM) to the medium significantly reversed CLT-induced p27 and p53 protein level increase and growth suppression. Our results suggest that CLT induces cell cycle arrest of colon adenocarcinoma HT29 cells via induction of p27 and p53, which may, at least in part, be mediated by alteration of intracellular $Ca^{2+}$ level.

Anatomical Observation of Vitrified and Glaucous Leaf from Rehmannia glutinosa Plant Produced in Vitro (지황 기내배양시 투명화된 잎과 정상잎간의 조직학적 관찰)

  • 백기엽;유광진;박상일;신성련
    • Korean Journal of Plant Tissue Culture
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    • v.24 no.6
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    • pp.323-327
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    • 1997
  • Addition of growth inhibitors such as ancymidol, ABA, chloromequat, and pachlobutrazol into MS medium had no effect to preventing vitrification in cultures of Rehmania glutinosa. Anatomical investigation revealed that vitrified thick leaf tissue in vitro had larger intercellular space with poor development of sponge and pallisade tissue compared to those of in vitro grown glaucous and field grown plants. In vitro grown glaucous leaf had smaller and round type stomata showing distinguishable guard and subsidiary cell than those of reestablished plantlets into soil whereas abnormal stomata and poor development of epicuticular wax on the surface of leaf was observed in verified plantlet.

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Effect of Interleukin-2 on Antitumor Response Against Subcutaneous Meth-A Tumor in Mice (마우스에서 Meth-A 종양세포에 대한 Interleukin-2의 항암효과)

  • 권오덕
    • Journal of Veterinary Clinics
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    • v.17 no.2
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    • pp.305-314
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    • 2000
  • Recombinant inteileukin-2 (IL-2) is a potent inductive stimulus for nitric oxide synthesis (NO.) and has been demonstrated as an antineoplastic agent in mice and human. But it is not let clear whether NO. can contribute to IL-2-induced therapeutic responses. Therefore, the current experiment was undertaken to clarify the effect of IL-2 on antitumor response against subcutaneous Meth-A tumor in mice. At the beginning of each experiment, normal BALB/c mice were injected subcuta-neously with $5{\times}10^6 Meth-A$ tumor cells. Some mice were implanted with osmotic minipumps con- taining 225 $\mu$l of 3.38 M $N^{\gamma}$ -monomethyl-L-arginine (MLA. an NOS inhibitor). Beginning on day 7, experimental groups were treated with a f-day course of IL-2 (50,000 lU,75,000 nJ,100,0007, 50,000 IU+MLA, 75,000 IU+MLA, 100,000 IU+MLA intraperitoneal injection every 12 hours for 5 days). The result of this experiment revealed that Meth-A tumor grew progressively in control mice. Intraperitoneal IL-2 treatment decreased tumor growth and prolonged survival. compared with con-trol mice. But no significant differences among 50.000 lU.75.000 lU and 100,000 lU of 7-2 treat-ment were observed. MLA administration prevented partially the decrease tumor growth and prolong survival of IL-2 treated mice compared with mice receiving IL-2 alone.

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Anticancer and Antimicrobial Activities of 13(E)-labd-13-ene-8α,15-diol from Brachyglottis monroi

  • Kim, Jong-Im;Choi, Hwa-Jung;Lee, Jae-Sook
    • Journal of Applied Biological Chemistry
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    • v.56 no.1
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    • pp.49-51
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    • 2013
  • In a previous study, we reported that 13(E)-labd-13-ene-$8{\alpha}$,15-diol (13E) possesses antiviral and anticancer activities. In this study, the anticancer and antimicrobial activities of 13(E) were evaluated against 4 cancer cell lines and 6 bacteria. 13(E) showed inhibitory effect on a variety of cancer cell lines. The $IC_{50}$ values was 8.3-21.3 ${\mu}g/mL$. 13(E) was the most effective growth inhibitor of murine leukaemia cell lines P388, producing approximately 8.3 ${\mu}g/mL$ of $IC_{50}$ in the cytopathic effect (CPE) method. 13(E) also inhibited the growth of the gram-positive bacteria (Staphylococcus aureus, Bacillus cereus and Listeria monocytogenes) and gram-negative bacteria (Vibrio parahaemolyticus, Escherichia coli and Salmonella enteritidis) with a range of minimum inhibitory concentration (MIC) values from 0.092 to 0.598 mg/mL and gram-negative bacteria were more sensitive to the compound (MIC, 0.092 mg/mL).

Role of glutamine synthetase as as regulator of nitrogenase in rhodopseudomonas sphaeroides D-230 (광합성 세균에 있어서의 질소고정효소 합성 조절자로서의 glutamine synthetase의 역할)

  • 이혜주
    • Korean Journal of Microbiology
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    • v.24 no.2
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    • pp.113-118
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    • 1986
  • Optimum temperature and pH of glutamine synthetase activity (E.C. 3.6.1.2.) of R. sphaeroides D-230 was $35^{\circ}C$ and 6.8, respectively. The adenylated state of GS in R. sphaeroides D-230 was stabilized by addition of 0.2mg/ml of cethyltrimethylammoniumbromide. Valine, histidine, proline, isoleucine, and lysine were good nitrogen source for the growth of R. sphaeroides D-230. The growth of R. sphaeroides D-230 in $N_2,\;NaNO_3\;or\;NH_4Cl$ as sole nitrogen source was lower than in any otherculture conditions. GS activity was inhibited, more or less, by various amino acid. THe relative inhibition rate of the enzyme by added 7mM arginine, $NH_4Cl,\;N_2,\;and\;NaNO_3$ was 63.8%, 26.79%, 6.24%, and 10.64%, drespectively. THe hydrogen evolution of R. sphaeroides D-230 grown in N-limited media was inhibited by 0.1mM MSX, irreversible GS inhibitor. GS activity was completely inhibited by 1.0mM MSX but ammonia released maximally at the same concentration of MSX. Ammonia release by added MSX was increased up to 1.0mM MS, but decreased above 1.0mM MSX. It is probably due to inhibition of nitrogenase actixity by MSX. Nitrogenase activity was not inhibited at low concentration of MSX. These results suggests that the inhibition of nitrogenase activity by ammonia is mediated by products of ammonia assimilation rather than by ammonia itself.

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Anti-cancer Effects of Luteolin and Its Novel Mechanism in HepG2 Hepatocarcinoma Cell (루테올린의 간암세포 성장 억제효능 및 새로운 작용기전)

  • Hwang, Jin-Taek;Yang, Hye-Jung
    • KSBB Journal
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    • v.25 no.6
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    • pp.507-512
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    • 2010
  • In this study, we investigated the ability of luteolin, a plant derived flavonoid on hepatocarcinoma cell growth using HepG2 cell culture system. We found that luteolin increased the Smac/DIABLO releases, a mitochondrial protein that potentiates apoptosis. Luteolin also induced either transcriptional activity or expression of PPAR-gamma, a target of cancer growth that PPAR-gamma agonist sensitizes to apoptosis in certain cancer types. To find the possible upstream target molecules of PPAR-gamma activated by luteolin treatment, we used compound C, a specific inhibitor of AMP-activated protein kinase. Pre-treatment of Compound C significantly restored the activation or expression of PPAR-gamma stimulated by luteolin. This result indicated that AMPK signaling might be involved in the activation or expression of PPAR-gamma signaling pathway stimulated by luteolin. Moreover, we also found that luteolin inhibited the insulin-stimulated Akt phosphorylation as well as AICAR, a specific AMPK activator. These results propose that luteolin significantly induces cancer cell death through modulating survival signal pathways such as PPAR-gamma and Akt. AMPK signaling pathway may be an upstream regulator for survival signal pathways such as PPAR-gamma and Akt stimulated by luteolin.

Rapamycin-resistant and torin-sensitive mTOR signaling promotes the survival and proliferation of leukemic cells

  • Park, Seohyun;Sim, Hyunsub;Lee, Keunwook
    • BMB Reports
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    • v.49 no.1
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    • pp.63-68
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    • 2016
  • The serine/threonine kinase mTOR is essential for the phosphoinositide 3-kinases (PI3K) signaling pathway, and regulates the development and function of immune cells. Aberrant activation of mTOR signaling pathway is associated with many cancers including leukemia. Here, we report the contributions of mTOR signaling to growth of human leukemic cell lines and mouse T-cell acute leukemia (T-ALL) cells. Torin, an ATP-competitive mTOR inhibitor, was found to have both cytotoxic and cytostatic effects on U-937, THP-1, and RPMI-8226 cells, but not on Jurkat or K-562 cells. All cells were relatively resistant to rapamycin even with suppressed activity of mTOR complex 1. Growth of T-ALL cells induced by Notch1 was profoundly affected by torin partially due to increased expression of Bcl2l11 and Bbc3. Of note, activation of Akt or knockdown of FoxO1 mitigated the effect of mTOR inhibition on T-ALL cells. Our data provide insight on the effect of mTOR inhibitors on the survival and proliferation of leukemic cells, thus further improving our understanding on cell-context-dependent impacts of mTOR signaling. [BMB Reports 2016; 49(1): 63-68]

Antifungal Activities of Copper(II) with Biosensitive Macrocyclic Schiff Base Ligands Derived from 4-Aminoantipyrine Derivatives

  • Gopalakrishnan, S.;Joseph, J.
    • Mycobiology
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    • v.37 no.2
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    • pp.141-146
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    • 2009
  • Novel copper(II) complexes have been synthesized from the macrocyclic Schiff bases derived from Knoevenagel condensed ${\beta}$-ketoanilides (obtained by the condensation of acetoacetanilide and substituted benzaldehydes), 4-aminoantipyrine and ophenylene diamine. The structural features have been determined from their analytical and spectral data. All the Cu(II) complexes exhibit square planar geometry. Their high molar conductance values support their 1 : 2 electrolytic nature. The magnetic moment data provide evidence for the monomeric nature of the complexes. The X-band ESR spectra of the |$CuL^1$|$(OAc)_2$ in DMSO solution at 300 and 77 K were recorded and their salient features are reported. The in vitro biological screening effects of the investigated compounds were tested against the bacterial species Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris and Pseudomonas aeruginosa and fungal species Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Rhizoctonia bataicola and Candida albicans by well diffusion method. A comparative study of inhibition values of the Schiff bases and their complexes indicate that complexes exhibit higher antimicrobial activity than the Schiff bases. Copper ions proved to be essential for the growth-inhibitor effect. The extent of inhibition appeared to be strongly dependent on the initial cell density and on the growth medium.

Vitexin, an HIF-1α Inhibitor, Has Anti-metastatic Potential in PC12 Cells

  • Choi, Hwa Jung;Eun, Jae Soon;Kim, Bang Geul;Kim, Sun Yeou;Jeon, Hoon;Soh, Yunjo
    • Molecules and Cells
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    • v.22 no.3
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    • pp.291-299
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    • 2006
  • Vitexin, a natural flavonoid compound identified as apigenin-8-C-${\beta}$-D-glucopyranoside, has been reported to exhibit antioxidative and anti-inflammatory properties. In this study, we investigated its effect on hypoxiainducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) in rat pheochromacytoma (PC12), human osteosarcoma (HOS) and human hepatoma (HepG2) cells. Vitexin inhibited HIF-$1{\alpha}$ in PC12 cells, but not in HOS or HepG2 cells. In addition, it diminished the mRNA levels of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF), smad3, aldolase A, enolase 1, and collagen type III in the PC12 cells. We found that vitexin inhibited the migration of PC12 cells as well as their invasion rates, and it also inhibited tube formation by human umbilical vein endothelium cells (HUVECs). Interestingly, vitexin inhibited the hypoxia-induced activation of c-jun N-terminal kinase (JNK), but not of extracellular-signal regulated protein kinase (ERK), implying that it acts in part via the JNK pathway. Overall, these results suggest the potential use of vitexin as a treatment for diseases such as cancer.

Microstructure and Electrical Properties of $SiO_2$-Doped Zinc Oxide Varistors ($SiO_2$가 첨가된 산화아연 바리스터의 미세구조 및 전기적 특성)

  • 남춘우;정순철
    • Electrical & Electronic Materials
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    • v.10 no.7
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    • pp.659-667
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    • 1997
  • The influence of SiO$_2$on the microstructure and electrical properties of zinc oxide varistor was investigated. Zn$_2$SiO$_4$third phase in the sintered body was found at grain boundaries, multiple grain junctions, and occasionally within ZnO grains. This phase acted as a grain growth inhibitor, which retard the grain growth of the ZnO matrix by impeding migration on the grain boundaries. As SiO$_2$ addition increases, average grain size decreased from 40.6${\mu}{\textrm}{m}$ to 26.9${\mu}{\textrm}{m}$ due to the pinning effect by Zn$_2$SiO$_4$ and drag effect by Si segregation at grain boundaries, the breakdown voltage consequently increased. When SiO$_2$ addition is increased, interface state density decreased, however, the barrier height increased by decrease of donor concentration, as a result, the nonlinear exponent increased and leakage current decreased. While, as SiO$_2$ addition increase, it was found that the apparent dielectric loss factor shows a tendency of decrease. Wholly, electrical properties of zinc oxide varistor can be said to be improved by SiO$_2$addition.

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