• Toxicological Research
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• 제20권1호
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• pp.21-29
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• 2004

We used cDNA microarray to assess gene expression profiles in hematopoetic cell line, U-937, exposed to low doses of ionizing irradiation. The 1,000 DNA elements on this array were PCR-amplified cDNAs selected from named human cancer related genes. According to the strength of irradiation, the levels of some gene expression were increased or decreased as dose-dependent manner. The gene expressions of Tubulin alpha, protein kinase, interferon-alpha, -beta, -omega receptor and ras homolog gene family H were significantly increased. Especially, Tubulin gene was shown 2.5 fold up-regulated manner under stress of 500 rad irradiation than 200 rad. On the other hand, fibroblast growth factor 12 and four and a half LIM domains, etc. were significantly down-regu-lated. Also, tumor protein 53(TP53) related genes that p53 inducible protein, tumor protein 53-binding protein looks of little significance as radiation sensitive manner. The radio-sensitivity of tubulin gene etc. that we proposed could be useful to rapid and correct survey for the bio-damage by exposure to low dose irradiation.

• IMMUNE NETWORK
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• 제11권6호
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• pp.348-357
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• 2011

Background: N-myc downstream-regulated gene 2 (NDRG2), a member of a newly described family of differentiation-related genes, has been characterized as a regulator of dendritic cells. However, the role of NDRG2 on the expression and activation of transcription factors in blood cells remains poorly understood. In this study, we investigated the effects of NDRG2 overexpression on GATA-1 expression in PMAstimulated U937 cells. Methods: We generated NDRG2-overexpressing U937 cell line (U937-NDRG2) and treated the cells with PMA to investigate the role of NDRG2 on GATA-1 expression. Results: NDRG2 overexpression in U937 cells significantly induced GATA-1 expression in response to PMA stimulation. Interestingly, JAK2/STAT and BMP-4/Smad pathways associated with the induction of GATA-1 were activated in PMA-stimulated U937-NDRG2 cells. We found that the inhibition of JAK2 activation, but not of BMP-4/Smad signaling, can elicit a decrease of PMA-induced GATA-1 expression in U937-NDRG2 cells. Conclusion: The results reveal that NDRG2 promotes the expression of GATA-1 through activation of the JAK2/STAT pathway, but not through the regulation of the BMP-4/Smad pathway in U937 cells. Our findings further suggest that NDRG2 may play a role as a regulator of erythrocyte and megakaryocyte differentiation during hematopoiesis.

• 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.

• 생명과학회지
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• 제18권1호
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• pp.96-102
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• 2008

이상의 연구 결과에 의하면 piceatannol의 처리에 의한 U937 세포의 증식억제는 세포주기 S기 arrest 및 apoptosis 유발과 뚜렷한 연관성이 있었다. 또한 piceatannol은 hTERT 및 TEP-1 유전자의 발현 저하와 연관된 telomerase 활성의 저하 효과도 나타내었으나, COXs의 발현 및 PGE2의 생성에는 큰 변화를 주지 못하였다. 따라서 본 연구의 결과는 암세포에서 높게 발현되는 telomerase 활성 조절제로서 piceatannol의 적용이 가능함을 보여주며, 이는 piceatannol의 항암작용을 이해하는데 매우 유용한 자료라 생각한다.

• 대한한방내과학회지
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• 제32권4호
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• pp.565-583
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• 2011

Objectives : This study investigated the biochemical mechanisms of anti-proliferative and pro-apoptotic effects of the water extract of Dan-Seon-Tang (DST) in human leukemia U937 cells. Methods : U937 cells were exposed to DST and growth inhibition was measured by MTT assay. Results : Exposure of U937 cells to DST resulted in the growth inhibition in a concentration-dependent manner. This inhibitory effect was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies, increased populations of apoptotic-sub G1 phase and induction of DNA fragmentation. The induction of apoptotic cell death in U937 cells by DST was associated with up-regulation of death receptor 4 (DR4) and down-regulation of Bid, surviving and cellular inhibition of apoptosis protein-2 (cIAP-2) expression. DST treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant degradation of caspase-3 substrate proteins such as poly (ADP-ribose) polymerase (PARP), phospholipase (PLC)-${\gamma}1$, ${\beta}$-catenin and DNA fragmentation factor 45/inhibotor of caspase activated DNAse (DFF45/ICAD). Furthermore, apoptotic cell death by DST was significantly inhibited by caspase-3 specific inhibitor z-DEVD-fmk, demonstrating the important role of caspase-3. Conclusions : These findings suggest that herb prescription DST may be a potential chemotherapeutic agent for the control of human leukemia U937 cells; further study is needed to identify the active compounds.

• 동의생리병리학회지
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• 제17권3호
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• pp.643-647
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• 2003

The Methylene Chloride(MC) fraction of Trichosanthis kirilowii Maxim has been investigated anti-tumor activities in vitro. The MC fraction of Trichosanthis kirilowii Maxim significantly inhibited the proliferation of human leukemic U937 cell with an IC50 of approximately 10μg/ml in a dose-dependent manner. We found that the MC fraction upregulated of caspase9 and caspase-3 activity and cleaved PARP expression but it didn't affect bax and bcl-2. which were demonstrated by western blot analysis. Taken together, these results exerted that the MC fraction suppessed human leukemic U937 cell proliferation by inducing apoptosis, suggesting the MC fraction of Trichosanthis kirilowii Maxim is possible to show anti-cancer activity in vivo.

• 생명과학회지
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• 제28권11호
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• pp.1321-1331
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• 2018

본 연구에서 N. commune으로부터 U937과 SK-HEP-1 세포에 대해 apoptosis를 유도하는 광과민성물질을 순수 분리하였다. N. commune을 dichloromethane : Methanol (1:1)로 추출하여 Hexane, EtOAc, MeOH로 분획하였다. 높은 광역학활성을 나타내는 EtOAc 분획물에서 NC-1을 분리하였으며, 분자량 870의 pheophytin a ($C_{55}H_{74}N_4O_5$)인 것으로 구조를 동정하였다. 광역학활성 조사는 NC-1을 $1.15{\mu}M$에서 $23.00{\mu}M$까지 5개의 농도를 처리하여 광을 조사하는 것과 조사하지 않는 조건으로 나누어 평가하였다. U937과 SK-HEP-1 두 세포에서 apoptotic body 형성, cell blebbing 등의 형태적 변화와 세포독성, caspase 활성, 세포핵의 응축, DNA 단편화 등이 광 의존적이며 농도 의존적으로 활성이 증가하였다. 추가적으로 유세포분석을 통한 apoptosis 유도의 정량적 분석 결과에서도 광조건에서 농도가 증가할수록 apoptosis 유도가 증가하는 것을 확인하였다. 이러한 결과를 통해 NC-1의 U937과 SK-HEP-1 세포에 대한 사멸은 광역학적 apoptosis에 의한 것임을 확인하였다. 본 연구 내용을 N. commune으로부터 광감각제 개발의 기초자료로 활용할 수 있을 것이다.

• 동의생리병리학회지
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• 제17권3호
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• pp.629-632
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• 2003

Scutellaria barbata has been used as a traditional Chinese Herb for treating liver, lung and rectal tumors. In the present study, cytotoxic effect of Scutellaria barbata MC fradtion was investigated and it was found to inhibit proliferation of human leukemic U937 cells with an IC50 of approximately 10 μg/ml in a dose-dependent manner. We also demonstrated that Scutellaria barbata MC fraction caused apoptosis in U937 cells. In the flow cytometric assay, the MC fraction-treated U937 cells showed an increase in hypo-diplold Sub G1 DNA contents. DNA fragmentation was observed by TUNEL assay. An increase of Bax:Bcl-2 ratio, activation of caspase-9, caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP) were demonstrated by western blot analysis. Taken together, these results exerted that the MC fraction suppressed human leukemic U937 cell proliferation by inducing apoptosis via the mitochondrial pathway.

• 생명과학회지
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• 제25권11호
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• pp.1255-1264
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• 2015

천궁(C. officinale)은 예로부터 민간처방 약재로 사용되었으며, 항염증, 항산화, 항암 및 신생혈관억제 등의 효능을 가지는 것으로 알려져 있다. 하지만 혈구암세포에서 apoptosis 유발과 관련된 분자생물학적 기전에 대해서는 명확히 밝혀져 있지 않다. 본 연구에서는 인체 혈구암세포인 U937 세포에서 천궁의 열수, 에탄올 및 메탄올 추출물(WECO, EECO 및 MECO)이 유발하는 항암효과 및 항암기전을 조사하였다. 먼저 WECO, EECO 및 MECO가 유발하는 증식억제 정도를 조사한 결과 EECO가 가장 뛰어난 효능을 가진다는 것을 알 수 있었으며, 이러한 현상이 apoptosis 유발에 의한 것임을 annexin-V 염색, apoptotic body 형성, DNA 단편화 및 MMP 소실 등을 통하여 확인하였다. EECO 처리에 의한 apoptosis 유발에는 DR4의 발현 증가와 함께 cIAP-1, Bcl-2 및 total Bid의 발현감소가 관여하였으며, caspases-3, -8 및 -9의 활성화와 함께 caspases-3의 기질 단백질인 PARP, β-catenin 및 PLC γ1의 단편화도 관찰되었다. 또한 EECO는 AMPK signaling pathway를 활성화시키는 것으로 나타났으며, AMPK 억제제인 compound C를 이용하여 AMPK의 활성을 억제하였을 경우 EECO에 의하여 유발되었던 apoptosis가 현저하게 감소되는 것으로 나타났다. 이상의 결과를 살펴볼 때 인체 혈구암세포인 U937 세포에서 EECO에 의하여 유발되는 apoptosis는 AMPK가 중요한 조절자로서 작용하는 것으로 생각된다.

• 약학회지
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• 제52권1호
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• pp.48-55
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• 2008

CD29 $({\beta}1-integrins)$ is one of major adhesion molecules involved in regulating cell adhesion, migration and morphological changes. In this study, we investigated the regulatory role of CD29 in monocytic functions using monocytic cell line U937 cells. CD29 was found to be one of highly expressed membrane proteins in U937 cells, according to flow cytometric analysis. The activation of CD29 by agonistic antibody MEM101A and extracellular matrix protein (ECM) fibronectin strongly induced cell-cell and cell-fibronectin adhesions. However, blocking antibodies to CD98 and CD147 showed different inhibitory features in these two adhesion events. Furthermore, U0126, an ERK inhibitor, only blocked cell-cell adhesion but not cell-fibronectin adhesion, indicating that cell-cell or cell-fibronectin adhesion events may be regulated by different molecular mechanisms. Meanwhile, CD29 activation also enhanced ROS generation but not phagocytic ability, and similarly radical scavenger N-acetyl-L-cysteine strongly blocked CD29-mediated cell-cell adhesion, implying that ROS may play a critical role in up-regulating cell-cell adhesion. Therefore, our data suggest that the activation of CD29 may be critically involved in regulating monocytic cell-mediated cell-cell adhesion and ROS generation.