• Journal of Microbiology and Biotechnology
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• 제13권4호
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• pp.607-612
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• 2003

To elucidate the action mechanism of MCS-C2, a novel analogue of toyocamycin and sangivamycin, its effect on the expression of cell cycle-related proteins in the human myelocytic leukemia cell line HL-60 was examined using Western blotting and a flow cytometric analysis. MCS-C2, a selective inhibitor of cyclin-dependent kinases, was found to inhibit cell growth in a time- and dose-dependent manner, and inhibits cell cycle progression by inducing the arrest at G1 and G2/M phases, in HL-60 cells. The flow cytometric analysis revealed an appreciable arrest of cells in the G2/M phase of the cell cycle after treatment with MCS-C2. The HL-60 cell population increased gradually from 13% at 0 h, to 28% at 12 h in the G2/M phase, after exposure to $2{\;}\mu\textrm{M}$ MCS-C2. Furthermore, Western blot analysis demonstrated that MCS-C2 induced the cell cycle arrest at G1 phase through the inhibition of pRb phosphorylation. Hypophosphorylated pRb accumulated after treatment with $5{\;}\mu\textrm{M}$ MCS-C2 for 12 h, whereas, the level of hyperphosphorylated pRb was reduced. Thus, treatment of the cell with MCS-C2 suppressed the hyperphosphorylated form of pRb with a commensurate increase in the hypophosphorylated form.

• Journal of Nutrition and Health
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• 제36권8호
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• pp.828-833
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• 2003

Dially disulfide (DADS), a component of garlic (Allium sativum), has been known to exert potent chemopreventive activity against various cancers. In this study, the synergistic effect of DADS and daunorubicin on the cytotoxicity of HL-60 cells, a human leukemia cell line, was investigated. DADS at 25 M greatly potentiated daunorubicin-induced cell death, decreasing cell viabilityto50%ofthe control. Daunorubicin-induced apoptosis was accompanied by the activation of caspase-3, the degradation of poly-(ADP-ribose) polymerase (PARP) and D4-GDI, and DNA fragmentation, which were blocked by pre-treatment with acetyl-Asp-Glu-Val-Asp- dialdehyde (Ac-DEVD-CHO). Treatment that combined 25 M DADS and 100 nM daunorubicin caused a similar degree of caspase-3 activation, PARP and D4-GDI degradation, and DNA fragmentation to that caused by treatment with 250 nM daunorubicin alone. These results indicate that combined therapy using daunorubicin with DADS, a component of food, and garlic can effectively decrease the therapeutic dose of daunorubicin, preventing the severe side effects of daunorubicin.

• Archives of Pharmacal Research
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• 제25권4호
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• pp.480-484
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• 2002

Costunolide has been reported to be a cytotoxic and chemopreventive agent. This work investigated the mechanism of the anti proliferative effect of costunolide and determined that it induced differentiation of the human leukemia cell line HL-60. Costunolide exhibited a potent antiproliferative activity against HL-60 cells. It was also found to be a potent inducer of differentiation in human leukemia derived HL-60 cells through the examination of differentiation markers, as assessed by the reduction of nitroblue tetrazolium, the increase in esterase activities and phagocytic activity, morphology change and the expression of CD14 and CD66b surface antigens. These results, accompanied by a decline in the expression of c-myc protein, suggest that costunolide induces differentiation of human leukemia cells to granulocytes and monocytes/macrophages lineage.

• 대한의생명과학회지
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• 제19권2호
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• pp.118-123
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• 2013

Tumor necrosis factor-alpha (TNF-${\alpha}$) is a proinflammatory cytokine that mediates the inflammatory response and immune functions, and modulates the proliferation, differentiation and cell death of cancer cells. The differential functions of TNF-${\alpha}$ in various human cells due to the formation of different stimulating pathway upon the binding of TNF-${\alpha}$ to its receptors. In the present study, we examined the different effects of TNF-${\alpha}$ on the survival and apoptosis between normal granulocytes and human myeloid leukemia HL-60 cells. Although TNF-${\alpha}$ did not affect on the constitutive apoptosis of granulocytes, TNF-${\alpha}$ strongly induced the apoptosis of HL-60 cells in a dose- and a time-dependent manner. TNF-${\alpha}$-induced apoptosis was occurred via the activation of caspase 8, caspase 9 and caspase 3/7 and the induction of ROS production in HL-60 cells. Also, BAY-11-7085, a NF-${\kappa}B$ inhibitor, blocked the TNF-${\alpha}$-induced apoptosis in HL-60 cells. NF-${\kappa}B$ may be involved in TNF-${\alpha}$-induced apoptotic signaling pathway in HL-60 cells. These results suggest that TNF-${\alpha}$ activates apoptotic pathways and its process depends on cell type and many cellular factors. A better understanding of the differential effect of TNF-${\alpha}$ on cell apoptosis and survival may provide important information that can be used to elucidate the specific inhibitory effect of TNF-${\alpha}$ on the cancer dis.

• 생명과학회지
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• 제8권2호
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• pp.162-166
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• 1998

전 골수성 백혈병 세초인 HL-60 세포를 model로 하여, 민간요법으로 사용되어져 부작용이 극히 적은 거승로 알려진 고려인삼의 구성 성분 중 주요성분이 ginseng (Panzx ginseng C.A. Meyer) saponin 및 ginsenoside Rh1, Rh2, Rh3, 비파 (Eriobotrya japonica L.) 잎의 성분들 중에서 항발암 및 항암성분으로 알려진 ursolic acid 및 oleanolic acid, 웅담중의 중요성분 성분인 lithocholoc acid 드잉 분화능력이 있는 지를 조사하고자 본 실험을 수행아였다. Retinoic acid를 처리한 결과 타 연구자들의 연구결과들처럼 높은 분화력을 관찰할 수 있었으며, dbcAMP 단독 처리군에서도 높은 분화효과를 나타냈었다. Dexamethasone 처리군에서는 분화효과를 거의 관찰할 수 없었으나,dexamethansone과 구조적으로 유사한 ursolic acid와 oleanolic acid는 보다 높은 분화력을 보였고 웅담성분의 중요성분인 lirhocholic acid는 높은 분화력을 나타냈었다. Ginseng saponin은 0.00375% (w/v)에서 20% 이상의 분화력을 보였으며, Ginsenoside Rh2와 Rh3는 높은 분화력을 나타냈다.

• Biomolecules & Therapeutics
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• 제7권1호
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• pp.22-28
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• 1999

Induction of apoptosis is considered to be the underlying mechanism that accounts for the efficiency of chemotherapeutic drugs. It has recently been proposed that doxorubicin (DOX) can induce apoptosis in human leukemic cells via the Fas/Fas Ligand (FasL) system. Comparison of Fas and FasL mRNA expression between drug- and anti-Fas antibody(Fas-Ab)- induced apoptosis was analyzed for examining the role of Fas/FasL system in the mediation of drug-induced apoptosis. After HL-60 cells were routinely cultured, MTT assay was performed for cytotoxicity test. Giemsa staining was carried out to monitor the apoptosis morphologically. By semiquantitative RT-PCR analysis, the expression of Fas and FasL at 4, 10, 24 hours was determined after DOX and Fas-Ab treatment. Dose-dependent cytotoxicity was induced by DOX-treatment, while Fas-Ab treatment showed the similar dose-dependent pattern but the cytotoxicity is not reached at LD$_{50}$ at 100 ng/ml concentration of Fas-Ab. In the 10ng/m1 DOX and 10ng/m1 Fas-Ab treated group, typical apoptotic cell morphology was shown such as fragmented nuclei and cell membrane budding in the Giemsa-stained slide. Fas mRNA expression was not changed significantly in the both groups. But, FasL mRNA expression was induced significantly at initial period of apoptosis. In this study, Fas/FasL interaction assumed to be involved in drug-induced apoptosis.s.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.382.3-382.3
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• 2002

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in the arteries. Monocytes/macrophages are involved in many aspects of the development of atheroscleotic plaques. It is known that the intercellular adhesion molecule-1 (ICAM-1) expressed preferentially on endothelial cells of atheroscleotic plaque. promotes local adhesion and transendothelial migration of monocytes, neutrophils. and lymphocytes. Using the human promyelocytic leukemia HL-60 cell line, we investigated the inhibitory effects of methoanol extracts of 175 plants on ICAM-1/LFA-1 mediated cell adhesion. Eight kinds of methanol extracts of tested plants inhibited PMA-induced homotypic aggregated cell adhesion. Eight kinds of methanol extracts of tested plants inhibited PMA-induced homotypic aggregation of HL-60 cells without cytotoxicity at the concentration of 6.25 ${\mu}$g/ml. $CHCl_3$ extracts (1.0 ${\mu}$g/ml) of Saururus chinensis and Chloranthus japonicus significantly inhibited agregation of HL-60 cells without cytoxicity.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.158.1-158.1
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• 2002

• 디지털융복합연구
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• 제13권8호
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• pp.543-548
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• 2015

본 논문은 야채수프의 인간 암세포 증식 억제효과를 살펴보는 데 목적이 있다. 본 연구는 일반적으로 사용되는 야채수프 (VS)와 브로콜리가 들어간 야채수프 (VSB), 토마토가 들어간 야채스프 (VST)를 이용하여 암세포 증식 억제효과를 살펴보았다. 인간 암세포주는 위암 (AGS)세포주, 급성 전골수성 백혈병 (HL-60)세포주, 폐암 (A549) 세포주를 사용하였으며 MTS방법으로 암세포 증식 억제를 확인하였다. 위암 세포주는 VSB, VST에서 암세포 증식 억제효과가 있었으며 VS에 비해 유의성이 있었다. 급성 전골수성 백혈병 세포주는 VST에서 유의성 있는 억제를 보였으며 폐암 세포주는 VSB에서 VS보다 탁월한 효과를 보였다. 혼합 야채스프는 기능성 소재로 활용과 융복합적인 웰리스를 위한 기초 자료로 활용이 가능하다고 사료된다.

• 미생물학회지
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• 제44권4호
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• pp.299-304
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• 2008

마이엘로이드 계열의 단핵세포는 인체세포거대바이러스(human cytomegalovirus, HCMV)의 잠복 부위로 알려져 있다. 다양한 세포에서 HCMV에 의한 세포주기의 촉진 또는 억제에 관한 연구는 많이 있었지만, 단핵세포에서의 연구는 거의 없는 상태이다. 이에 본 연구에서는 단핵세포에 HCMV가 감염되면 세포주기에 어떤 변화가 나타나는지 알아보고자 하였다. Propidium iodide를 이용한 유세포 분석을 통한 세포주기 분석에서 HCMV에 감염된 THP-1 세포에서는 G0-G1기가 증가하고, 그만큼 S가 감소함을 보았다. 반면 HL-60 세포에서는G0-G1기와 S기의 상대적인 비율에 큰 변화가 없었다. BrdU 유입 실험에서 THP-1세포의 DNA 합성이 HCMV 감염에 의해 억제됨을 알 수 있었다. 세포주기의 G1기에서 S기로의 전환을 억제하는 p21 단백질은HCMV에 감염된 THP-1 세포에서는 발현이 유도되었지만 HL-60 세포에서는 거의 발현이 되지 않았다. 따라서 HCMV는 promocyte THP-1 세포에서 p21 단백질의 유도에 의해 세포주기를 G0-G1기에서 억류함에 따라 세포중식을 억제하는 것으로 생각된다.