• 생명과학회지
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• 제17권4호
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• pp.552-560
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• 2007

본 연구에서는 인체백혈병세포 U937에서 HDAC 저해제에 의한 증식억제, 세포주기 교란 및 apoptosis 유도에 미치는 Bcl-2 유전자의 영향에 관하여 조사하였다. 이를 위하여 U937/vector 및 U937/Bcl-2 세포주를 대상으로 대표적인 HDAC 저해제인 TSA 및 Na-B 처리에 의한 세포 증식 및 생존율에 미치는 영향을 조사한 결과, TSA에 의한 U937 세포의 증식억제 및 생존율의 감소는 Bcl-2의 과발현에 의하여 차단되는 효과를 보였으나, Na-B는 U937/vector 및 U937/Bcl-2세포사이에 큰 변화를 보이지는 않았다. 세포주기 교란효과에서 Na-B는 TSA에 비하여 유의적인 차이를 보이지 못하였으며, 이는 TSA에 의한 apoptosis가 U937/Bcl-2 세포에서는 억제되었으나, Na-B에 의한 apoptosis는 Bcl-2의 과발현에 의하여 차단되지 못한 것과 연관성이 있는 결과였다. 또한 TSA에 의한 apoptosis 유발의 Bcl-2에 의한 차단 효과는 TSA에 의하여 활성화된 caspase의 활성 억제, Bcl-2 발현 자체의 완화 등 apoptosis 조절 인자들의 발현 및 활성 변화에 기인 된 것임을 알 수 있었다.

• Toxicological Research
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• 제19권3호
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• pp.197-203
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• 2003

Apicidin, a histone-deacetylase inhibitor, has been successfully used to inhibit the growth of cancer cells. In this study, the apoptotic potential and mechanistic insights of apicidin were investigated in human myeloid leukemia U937 cells. Treatment of U937 cells with apicidin resulted in a decrease of cell viability with apoptotic characteristics, including chromatin condensation and ladder-pattern fragmentation of genomic DNA. Apicidin converted the procaspase-3 protease to catalytically active effector protease, resulting in subsequent cleavage of poly (ADP-ribose) polymerase (PARP) and inhibitor of caspase-activated deoxyribonuclease (ICAD). In addition, apicidin induced the activation of caspase-9 protease and the cytosolic release of mitochondrial cytochrome c with mitochon-drial membrane potential transition. Moreover, apicidin transiently increased the expression of Fas and Fas ligand proteins. Taken together, the results suggest that apicidin induces apoptosis of U937 cells through activation of intrinsic caspase cascades and Fas/FasL system with mitochondrial dysfunction.

• BMB Reports
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• 제36권5호
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• pp.520-523
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• 2003

The proliferation and differentiation signals of myelogeneous U937 cells are provided by extracellular stimuli, such as lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA). In a DNA-native-polyacrylamide gel assay system, we demonstrated that a particular nuclease activity is expressed in PMA-stimulated U937 cells and secreted into the culture medium. The nuclease activity was induced in U937 cells by LPS treatment, while the secretion of the enzyme was undetected in the culture medium. Therefore, it is likely that the expression and secretion of the particular nuclease in U937 cells are controlled by extracellular stimulations, such as PMA and LPS treatment.

• 한국환경성돌연변이발암원학회지
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• 제22권1호
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• pp.54-59
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• 2002

We have used cDNA microarray hybridization to identify gene regulated in response to gamma-irradiation in U-937 cell. The cDNA-chip was composed entirely of 1,000 human cancer related gene including apoptosis and angiogenesis etc. In gamma-irradiated U-937 cell, highly charged protein, ribosomal protein L32, four and a half LIM domains 3, lipocalin 2 (oncogene 24p3) and interleukin 15, ataxia telangiectasia mutated (includes complementation groups A, C and D) genes showed increased level of its transcription, and cell division cycle 25A, dihydrofolate reductase, topoisomerase (DNA) II beta(180kD), kinase suppressor of ras and strarigin genes showed reduced level of its transcription compared to untreated U-937 cell. The significant change of level of transcription was not found in well-known ionizing radiation(IR)-responsive gene, such as transcription factor TP53 and p53 related gene, except ataxia telangiectasia mutated gene.

• International Journal of Oral Biology
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• 제37권3호
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• pp.91-102
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• 2012

Bcl-2 protects tumor cells from the apoptotic effects of various anti-neoplastic agents. Increased expression of Bcl-2 has been associated with a poor response to chemotherapy in various malignancies, including leukemia. Hence, bypassing the resistance conferred by anti-apoptotic factors such as Bcl-2 represents an attractive therapeutic strategy against cancer cells, including leukemic cells. This study was undertaken to examine whether the anticancer drug, cisplatin and the synthetic chenodeoxycholic acid (CDCA) derivative, HS-1200 show anti-tumor activity in U937 and U937/Bcl-2 cells. Viability assays revealed that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells. Various apoptosis assessment assays further demonstrated that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells by inducing apoptosis. In addition HS-1200, but not cisplatin, overcomes the anti-apoptotic effects of Bcl-2 in Bcl-2 over-expressing human leukemic cells (U937/Bcl-2 cells). Notably, we observed that the HS-1200-induced formation of mature promyelocytic leukemia (PML) nuclear bodies (NBs) correlates with a suppression of the anti-apoptotic effects of Bcl-2 in human leukemic cells over-expressing this protein (U937/Bcl-2 cells). Furthermore, HS-1200 was found to induce the association between PML and SUMO-1, Daxx, Sp100, p53 or CBP in the aggregated PML-NBs of U937/Bcl-2 cells. Thus, PML protein and the formation of mature PML-NBs could be considered as therapeutic targets that may help to bypass the resistance to apoptosis conferred by Bcl-2. Elucidating the exact mechanism by which PML regulates Bcl-2 will require further work.

• 한국식품영양과학회지
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• 제23권5호
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• pp.799-804
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• 1994

천연물에서 직접적인 암세포 살해능을 가지며, 동시에 중증의 백혈구 감소증을 억제시킬 수 있는 물질을 탐색하기 위하여 암세포주인 U937 human lymphoma cell과 정상면역 세포인 lymphocyte에 대한 권백 수침 엑기스의 암세포 살해능과, 현재 임상에서 응용되고 있는 화학요법제인 retinoic acid, doxorubicine, cyclopho-sphamide와의 병용요법이 암세포(U937)와 정상세포(lymphocyte)에 미치는 영향을 MTT 분석법을 이용하여 비교 관찰하여 다음과 같은 결과를 얻었다. 권백 수침 엑기스 단독첨가시 권백 수침 엑기스는 암세포인 U937 human iymphoma cell의 성장을 유의적으로 억제시켰으며, 정상면역세포인 lymphocyte에는 영향을 미치지 않았따. 권백 수침 엑기스와 호학요법제를 병용 첨가시 화학요법제를 단독 처리했을 때 보다 권백 수침 엑기스(1mg/ml)와 화학요법제를 병용하였을 때, U937의 세포살해능의 현저히 증가되었고, 한편 lymphocyte의 세포살해능은 감소하였다. 이상의 결과에서 화학요법제와 권백을 병용 투여함으로서 암세포 살해능은 증가되고, 정상세포 살해능은 감소되었으므로 화학요법제의 가장 큰 부작용인 immunosupression 중 $leucopeenia^{20~30}$를 감소시킬 수를 감소시킬 수 있을 것으로 사료된다.

• 동의생리병리학회지
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• 제25권1호
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• pp.29-36
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• 2011

Nardostachyts chinensis (N. chinensis) belonging to the family Valerianaceae has been used to elicit stomachic and sedative effects. The MAPKs are serine/threonine kinases involved in the regulation of various cellular responses, such as cell proliferation, differentiation and apoptosis. The PKC also plays a key role in regulating the response of hematopoietic cells to both physiological and pathological inducers of proliferation and differentiation. This study investigated the signaling pathways on the U937 cell differentiation induced by N. chinensis. N. chinensis induced the differentiation of U937 cells, as shown by increased of differentiation surface antigen CD11b. Activation of ERK increased time-dependently in differentiation of U937 cells induced by N. chinensis, but activations of JNK and p38 were unaffected. Inhibitor of ERK (PD98059) significantly reduced CD11b expression induced by N. chinensis in U937 cells. In addition, N. chinensis increased protein level of PKC ${\beta}$I and PKC ${\beta}$II isoforms, but the protein level of PKC ${\alpha}$ and PKC ${\gamma}$was constant. PKC inhibitors (GF 109203X and H-7) inhibited U937 cell differentiation and the ERK activation induced by N. chinensis. These results indicated that PKC and ERK may be involved in U937 cell differentiation induced by N. chinensis.

• 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.

• 동의생리병리학회지
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• 제17권2호
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• pp.293-296
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• 2003

Prunellae Spica is a flower petal of Prunella vulgaris var. lilacina used for treatment of lymphoma, breast cancer, hepatitis and pathological fluid related diseases in oriental medicine. We tried to evaluate the mechanism of Prunellae Spica in the treatment of cancer. The ethyl acetate layer of Prunellae Spica showed a good cytotoxicity on U937 cells with IC50 of 8 ug/ml. It induced apoptosis in U937 dose-dependently by cell cycle analysis following PI staining. We also confirmed it induced DNA fragmentation in U937 cells from the concentration of 10 ug/ml. From western blot assay we observed the ethyl acetate layer of Prunellae Spica downregulated procaspase-3 and cleaved PARP in a dose dependent manner, whereas it didn't affect bax and bcl-2. Taken together, these results indicate the ethyl acetate layer of Prunellae Spica can induce apoptosis in U937 cells suggesting it can be potently applied to cancer.

• 한국식품위생안전성학회지
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• 제11권1호
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• pp.71-75
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• 1996

In order to study the antitumoral effect of Selaginella tamariscina extracts, the cytotoxicities to human histiocytic leukemia cells (U937) and lymphocyte were measured by MTT method. The water extract of Selaginella tamariscina was partitioned into chloroform (CHCl3), ethylacetate (EtAc), n-butanol (BuOH) and water (H2O), successively. CHCl3, EtAc and BuOH fractions of Selaginella tamariscina showed the cytotoxicity to the U937 cells but they had effect on the cytotoxicity of lymphocyte under the same conditions. The tumor-specific cytotoxicity of Selaginella tamariscina fractions migh have been attributed to their genotoxic effect on actively proliferating cells. The expression of p53 tumor suppressor gene was then evaluated by northern blotting. The increased expression of p53 was induced by Selaginella tamariscina fraction V but no expression of p53 was induced by CHCl3, EtAc, and BuOH fractions of Selaginella tamariscina water extract (fraction V) should be required for the cytotoxcity on U937 and the other fractions of Selaginella tamariscina mediated the U937 disruption.