• 대한한의학방제학회지
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• 제18권1호
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• pp.121-132
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• 2010

Inflammatory reaction is characterized by over-production of inflammatory mediators due to an up-regulation of inflammatory pathways, which produce pro-inflammatory mediators, such as interleukin-1beta (IL-$1{\beta}$), IL-6, tumour necrosis factor alpha (TNF-$\alpha$), prostaglantin $E_2$ ($PGE_2$), and nitric oxide (NO) in U937 cells. We investigate the anti-inflammatory effects of water extracts from Lonicerae Flos and Scutellariae Radix in lipopolysaccharide (LPS)-stimulated U937 cells. Each extract suppressed the production of inflammatory mediators (NO, IL-$1{\beta}$, TNF-$\alpha$, and $PGE_2$) and the expression of inducible NO synthase and cyclooxygenase-2 in LPS- stimulated U937 cells in a dose-dependent manner. These suppressive effects were synergistically increased by their combination. Their combination extract also inhibited NF-${\kappa}B$-DNA complex of NF-${\kappa}B$ binding activity and translocation of NF-${\kappa}B$ from cytosol to nucleus. These results suggest that the combination of water-extractable components of Lonicerae Flos and Scutellariae Radix may be useful for therapeutic drugs against inflammatory immune diseases, probably by suppressing the production of inflammatory mediators.

• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.335-345
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• 2009

A major source of paeoniflorin (PF) which was from the Paeonia lactiflora root, has been used as a herbal medicine in East Asia for its antiallergic, antiinflammatory, and immunoregulatory effects. However, only few details are known about the mechanism of apoptosis induced by this compound. The present study was undertaken to further elucidate the molecular mechanism of apoptosis and the changes of gene expression elicited by PF using DNA microarrays and computational gene-expression analysis tools in human leukemia U937 cells. A comparative global transcription analysis between treatment with PF and anisomycin (AM) that induces apoptosis in U937 cells revealed that c-Jun-$NH_2$-kinase (JNK) pathway related genes were less expressed in PF-treated cells. Elucidation of the mechanisms by which PF conducts its anti-cancer activities through comparative analysis of the gene expression is necessary to provide a solid foundation for its use as a promising agent in prevention and treatment strategies.

• Archives of Pharmacal Research
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• 제28권6호
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• pp.685-690
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• 2005

We recently reported that the ginseng saponin metabolite, compound K (20-O-$\beta$-D-glucopyra-nosyl-20(S)-protopanaxadiol, IH901), inhibits the growth of U937 cells through caspase-dependent apoptosis pathway. In this study, we further characterized the effects of compound K on U937 cells and found that, in addition to apoptosis, compound K induced the arrest of the G1 phase. The compound K treated U937 cells showed increased p21 expression; an inhibitory protein of cyclincdk complex. The up-regulation of p21 was followed by the inactivation of cyclin D and the cdk4 protein, which act at the early $G_1$ phase, and cyclin E, which acts at the late $G_1$ phase. Furthermore, compound K induced the activation of JNK and the transcription factor AP-1, which is a downstream target of JNK. These findings suggest that the up-regulation of p21 and activation of JNK in the compound K treated cells contribute to the arrest of the $G_1$ phase.

• Journal of Microbiology
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• 제40권3호
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• pp.224-229
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• 2002

The effect of human cytomegalovirus (HCMV) on three human monocyte cell lines at different stages of differentiation was investigated. While the viability of HL-60 cells or U-937 cells was not significantly affected by HCMV infection, the viability of THP-1 cells was reduced. Acridine orange/ethidiurn bromide staining revealed that the reduction of THP-1 cell viability was due to increased apoptotic death following HCMV infection. Apoptosis in HL-60 cells was not affected by HCMV infection, and induction of apoptosis of U-937 cells by HCMV was intermediate between HL-60 and THP-1 cells. Since HL-60 cells are the least differentiated and THP-1 cells are the most differentiated, the induction of apoptosis of human monocytes appears to be related to the degree of cell differentiation. Flow cytometric and confocal microscopic studies using fluorescent calcium indicator Fluo-3 suggested a significant increase in intracellular free calcium concentration (［Ca$\^$2+/］i) in THP-1 cells undergoing apoptosis by HCMV infection. Again ［Ca$\^$2+/］i in HCMV-infected HL-60 cells was not critically altered, and that in HCMV-infected U-937 cells was intermediate between THP-1 cells and HL-60 cells. Calcium influx blockers such as verapamil and nifedipine partially reversed HCMV-induced apoptosis in THP-1 cells.

• 한국식품영양과학회지
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• 제23권3호
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• pp.443-452
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• 1994

This study describes the effects of novel1, 25-dihydroxyvitamin D$_3$ analong[1,25(OH)$_2$-16ene-23yne-26, 27-F6-D$_3$] on proliferation of the human histiocytic lymphoma cell line U937 in vitro. We also examined the expression of c-myc oncogene in U937 cells was apparently inhibited to 62% and 87% of the control level after 4 days in the presence of 10-8M and 10-7 M of this analog, respectively. This compound morpholgically and functionally differentiated U937 cells to nonocyte-macrophage phenotype showing the increase of adherence ability to surface and a decrease of N/C ratio in Giemsa staining . Especially, nonspecific esterase activity which is a marker of cell differentiation to monocyte-macrophage was positive, and production of the positive stained cells increased in a dose dependent fashion . The expression of c-myc oncogene by 1, 25(OH)$_2$D$_3$ analog(10-7 M) was reduced by 60% at the mRNA level as determined by Northern blotting. The effects of this novel analog on cell proliferation and cell differentiation may open op new therapeutic strategies for human disorders such as psoriassis and may provide a tool to understand the mechanism of action of vitamin D$_3$ seco-steroids in malignancy.

• 한국식품영양과학회지
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• 제24권1호
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• pp.1-9
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• 1995

1, 25(OH)2-23ene-D3 is a novel vitamine D3 analog which has a double bond between C-23 and C-24. We describe the effects of this analog on cell differentiation and cell proliferation in vitro using the human histiocytic lymphoma cell line U937, and on calcium metabolism in rats in vivo. In the present investigation 1, 25(OH)2-23ene-D3 was compared to the natural metabolite of vitamin D3, 1$\alpha$, 25-dihydroxycholecalciferol[1, 25(OH)2-23ene-D3 was more potent than 1, 25(OH)2-23ene-D3 for inhibition of proliferation and induction of differentiation of U937 cells. Especially, its effect on induction of differentiation, as measured by superoxide production and nonspecific esterase(NSE) activity, was about 20-fold more potent that 1, 25(OH)2-23ene-D3. This analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ratio in Giemsa staining and the increase of adherence ability to surface. Intraperitoneal administration of 1, 25(OH)2-23ene-D3 to rats showed that the compound had at least 50 times less activity than 1, 25(OH)2-23ene-D3 in causing hypercalcemia and hypercalciuria. The strong direct effects of 1, 25(OH)2-23ene-D3 on cell proliferation and cell differentiation, coupled with its decreased activity of calcium metabolism make this compound an interesting candidate for clinical studies including patients with leukemia, as well as several skin disorders, such as psoriasis.

• 동의생리병리학회지
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• 제20권2호
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• pp.358-364
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• 2006

To investigate the possible mechanism of Drynariae Rhizoma extracts as a candidate of anti-cancer drug, I examined the effects of Drynariae Rhizoma extracts on the apoptosis of U937 cell line. MTT assay, flow cytometric analysis, SDS-polyacrylamide gel electrophoresis, Western blot analysis, and RT-PCR were performed. Drynariae Rhizoma extracts treatment reduced the cell viablilty of U937 cells in a dose-dependent manner, which was associated with induction of apoptotic cell death. Drynariae Rhizoma extracts treatment also reduced the levels of Bcl-xL anti-apoptotic protein expression and increased the levels of caspase-3, p53, pro-apoptotic protein, in U937 cells. RT-PCR data revealed that the level of bcl-2, bcl-xL mRNA expressions decreased in a dose-dependent manner. These findings suggest that Drynariae Rhizoma extracts may have induction of apoptotic cell death via regulation of several growth regulatory gene products. The abbreviations used are: FBS, fetal bovine serum; PBS, phosphate buffered saline; PI, propidium iodide; OD, optical density; DiOC6, 3,3-dihexyloxa carbcyanine iodide; MTT, 3 [4-5-dimethylthiazol-2-yl] -2-diphenyltetrazolium bromide.

• BMB Reports
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• 제40권6호
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• pp.1009-1015
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• 2007

In this communication, we report the efficacy of $\beta$-carotene towards differentiation and apoptosis of leukemia cells. Dose ($20{\mu}M$) and time dependence (12 h) tests of $\beta$-carotene showed a higher magnitude of decrease (significance p < 0.05) in cell numbers and cell viability in HL-60 cells than U937 cells but not normal cell like Peripheral blood mononuclear cell (PBMC). Microscopical observation of $\beta$-carotene treated cells showed a distinct pattern of morphological abnormalities with inclusion of apoptotic bodies in both leukemia cell lines. When cells were treated with $20{\mu}M$ of $\beta$-carotene, total genomic DNA showed a fragmentation pattern and this pattern was clear in HL-60 than U937 cells. Both the cell lines, on treatment with $\beta$-carotene, showed a clear shift in $G_1$ phase of the cell cycle. In addition the study also revealed anti-oxidant properties of $\beta$-carotene since there was reduction in relative fluorescent when treated than the control at lower concentration. Collectively this study shows the dual phenomenon of apoptosis and differentiation of leukemia cells on treatment with $\beta$-carotene.

• 한국식품과학회지
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• 제34권1호
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• pp.114-117
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• 2002

연교의 메탄올 추출물로부터 caspase 저해물질을 분리하였으며, ESI-MS, $^1H-NMR$, $^13C-NMR$, DEPT 등의 기기분석 자료에 의하여 rengyolone으로 동정하였다. 이 물질은 $IC_{50}\;6.25\;{\mu}g/mL$의 농도에서 etoposide가 처리된 U937 세포주의 caspase-3 유도 저해를 나타내었다. 또한 rengyolone은 $Interleukin-1{\beta}$가 처리된 D10S 세포에서 caspase-1의 유도저해활성을 나타내었으며, $IC_{50}$값은 $7.5\;{\mu}g/mL$이었다.

• 생명과학회지
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• 제17권12호
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• pp.1709-1716
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• 2007

본 연구에서는 몇 가지 암세포를 대상으로 마늘 열수추출물(WEAS)의 항암활성을 조사하였으며, 비교적 높은 감수성을 보인 백혈병세포를 대상으로 세포증식억제가 apoptosis 유도와 연관성이 있음을 제시하였다. WEAS에 의한 U937 세포의 apoptosis 유도는 세포주기 G2/M arrest와 연관성이 있었으며, 다양한 apoptosis조절 유전자들의 발현 변화를 동반하였음을 확인하였다. 이러한 apoptosis조절 인자들의 발현변화는 미토콘드리아 막 전위의 소실과 연관성이 있었으며, WEAS에 의한 암세포의 G2/M arrest에 의한 apoptosis 유발에 ROS가 중요한 조절자로 작용함을 알 수 있었다.