• 생명과학회지
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• 제18권1호
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• pp.75-83
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• 2008

인체 DNA topoisomerase는 DNA를 단일 또는 두 가닥을 일시적인 절단을 촉매하여 DNA의 topological 문제를 조절함으로써, DNA 복제, 전사, 재조합과 유사분열 과정 등에 관여한다. 이 효소는 많은 항생, 항암제의 표적효소로서 널리 알려져 있으며, 이들 유도체를 이용한 다양한 억제제의 개발과 임상적 응용에 관한 연구가 활발하게 진행되고 있다. 본 실험에서는 인체 백혈병 HL-60 세포에서 topoisomerase 억제제가 topoisomerase 기능 활성과 유전자 발현을 조절하는지를 규명하기 위하여 본 연구를 수행하였다. 연구 방법은 HL-60세포에 topoisomerase type I과 type II의 대표적 억제제인 10-hydroxycamptothecin (10-CPT)과 doxorubicin을 투여한 후 total RNA를 분리하였고, 10K-oligo-nucleotide microarray 방법으로 분석하여 유전자의 발현 양상을 조사하였다. 연구 결과에 의하면 10-CPT 또는 doxorubicin을 투여한 HL-60세포에서의 유전자 발현 양상은 주로 signal transduction, cell adhesion, cell cycle, cell growth, cell proliferation, cell differentiation, transcription 및 immune response 등과 관련이 있었다. Topoisomerase type I의 억제제인 10-CPT를 HL-60 세포주에 투여 하였을 때 type I으로 분류되는 topoisomerase III${\alpha}$, III${\beta}$ 및 I의 발현은 증가하였으나 type II인 topoisomerase II${\alpha}$와 II${\beta}$의 유전자의 발현은 감소되었다. 반대로 type II의 억제제인 doxorubicin을 투여하였을 때는 앞의 결과와 상반된 topoisomerase II${\alpha}$와 II${\beta}$의 유전자의 발현이 현저히 증가되었으며, topoisomerase III${\alpha}$와 III${\beta}$의 mRNA의 발현은 약간 감소하는 양상을 보였으나 의미 있는 차이는 없었다. 이 연구 결과는 앞으로 항암제의 기전을 밝히고 약물에 대한 치료 반응을 예측하고 새로운 약제 개발에 기초자료가 될 것으로 여겨진다.

• 대한수의학회지
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• 제60권2호
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• pp.79-83
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• 2020

Fenbendazole (FBZ) is a benzimidazole anthelmintic that has been widely used in treatments for gastrointestinal parasites including pinworms and roundworms in animals. Recently, some studies demonstrated that FBZ has anti-cancer effects related to disruption of microtubule polymerization. In this study, we investigated whether FBZ has anti-cancer activity in HL-60 cells, a human leukemia cell line, and assessed its relationship with the production of reactive oxygen species (ROS). FBZ treatment at 0.25-1 μM significantly decreased the metabolic activity of HL-60 cells. The mitochondrial membrane potential of FBZ-treated HL-60 cells decreased in a concentration-dependent manner. Apoptosis analysis using annexin V-FITC/propidium iodide staining demonstrated that 1 μM FBZ increased the percentages of cells in apoptosis and necrosis. In addition, Hoechst 33342 staining showed the presence of broken nuclei in HL-60 cells treated with 0.5 and 1 μM FBZ. To investigate the anti-cancer mechanism of FBZ, HL-60 cells were treated with FBZ in the absence or presence of N-acetyl cysteine (NAC), an inhibitor of ROS production. NAC significantly recovered the decreased metabolic activity of HL-60 induced by 0.5 and 1 μM FBZ treatments. This study provides evidence that FBZ has anti-cancer activity in HL-60 cells provided, in part, via ROS production.

• 동의생리병리학회지
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• 제23권6호
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• pp.1314-1319
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• 2009

In previous study, we have shown that continentalic acid (CA) isolated from Aralia continentalis induced the growth inhibition and apoptosis in HepG2 cells. In this study, we examine the effects of CA from A. continentalis on growth inhibition and apoptosis induction in human leukemia HL-60 and mouse fibroblast NIH 3T3 cell lines. The results demonstrated that CA decreased cell growth of leukemia HL-60 cells but not human HaCaT keratinocytes, assessed with the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and LDH (lactate dehydrogenase) assay. Flow cytometric analysis of mouse fibroblast cell lines exposed to CA showed that apoptotic cells increased in a time- and dose-dependent manner. Treatment with CA decreased the number of normal cells and increased the number of early apoptotic and late apoptotic cells in a dose-dependent manner. The induction of apoptosis in mouse cell lines by CA was mediated through the activation of caspase-3, Bak, and Bax and the down-regulation of Bcl-2. Our results suggest that CA efficiently induces apoptosis in human leukemia cells.

• Bulletin of the Korean Chemical Society
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• 제31권12호
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• pp.3777-3781
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• 2010

The anticancer effect and apoptotic mechanism of a novel indole derivative AC-264, a lead derived from a chemical library, were investigated in human promyelocytic leukemia HL-60 cells. HL-60 cells treated with AC-264 at various concentrations showed the morphological features of apoptosis, such as plasma membrane blebbing and cell shrinkage. AC-264 exhibited cytotoxic effect in various cancer cell lines with different degrees of potency. Especially, AC-264 was effective on increasing the population of apoptotic cells in HL-60 cells, as detected by the number of cells stained with Annexin V and PI. Furthermore, AC-264 activated caspase-3 enzyme activity and induced internucleosomal DNA fragmentation. These results indicated that AC-264 produces anti-cancer effect via apoptotic cell death by activating caspase-3 and inducing internucleosomal DNA fragmentation in HL-60 cells.

• Toxicological Research
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• 제15권1호
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• pp.19-25
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• 1999

(+)-Catechin inhibited the growth and induced the differentiation of HL-60 human leukimia cells. The degree of a differentiation by (+)-catechin during the differentiation, the expression assay, To understand the molecular mechanism of (+)-catechin during the differentiation, the expression level of oncogenes was detected by Northern blot analysis. c-Myc mRNA level was reduced after treatment with (+)-Catechin (10-4), however, the expression of c-jun was increased with a concentration dependent manner in HL-60 cells. These results showed that the differentiation and antiproliferation of HL-60 cells against (+)-Catechin was related to the reduction of c-myc and the induction of c-jun expression.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.166.3-167
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• 2003

Helenalin, a cell-permeable pseudoguainolide sesquiterpene lactone, is a potent anti-inflammatory agent that inhibits $NF-{\kappa}B$ DNA binding activity by selectively alkylating the p65 subunit of $NF-{\kappa}B$. Transcription factors such as $NF-{\kappa}B$ provide powerful target of drugs to use in the treatment of cancer. Human promyelocytic leukemia HL-60 cells are differentiated into monocytic or granulocytic lineage when treated with 1,25-dihydroxyvitamin $D_3{\;}[1,25-(OH)_2D_3]$ or all-trans-retinoic acid (ATRA), respectively. (omitted)

• 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.318.1-318.1
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• 2002

We found that 23-hydroxyursolic acid, triterpenoid was isolated from Cussonia bancoensis have a significant cytotoxic activity against HL -60 human promyelocytic leukemia cells. The IC of 23-hydroxyursolic acid was 32.83 $\mu$M. These anti-proliferative activity was due to induction of apoptosis. The effect of apoptosis was identified by DNA laddering, DAPI assay. PI staining, and Annerxin V-FITC binding assay. (omitted)

• 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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.82-82
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• 2003

The present study was undertaken to examine the cytotoxic effect of extract of Eurya emarginata against cancer cells and to develop an anti-cancer agent using components of its leaves. The crude extract of its leaves markedly inhibited the growth of leukemia cells including HL-60. When the HL-60 cells were treated with the extract, DNA fragmentation, morphologic changes and sub-Gl hypodiploid cells were observed. Therefore, the inhibitory effect of E. emarginata on the growth of the HL-60 cells appears to arise from the induction of apoptosis. Moreover, the extract markedly reduced c-Myc expression in a time-dependent manner. Eutigoside C showing the cytotoxic effect was isolated from the leaves of E. emarginata. Eutigoside C reduced the Bcl-2 protein and mRNA levels in a time-dependent manner, whereas the Bax protein and mRNA expression levels were slightly increased. When HL-60 cells were treated with eutigoside C, the release of cytochrome C from mitochondria into the cytosol was observed. Also, the expressions of the active forms of caspase 9 and 3 were increased and the activation of caspase 3 was demonstrated by the cleavage of Poly(ADP-ribose) polymerase, a vital substrate of effector caspase. The results indicate that the eutigoside C from E. emarginata induce apoptosis of HL-60 cells via the down-regulation of Bcl-2 expression and activation of caspases.

• 동의생리병리학회지
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• 제19권6호
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• pp.1636-1639
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• 2005

To develop novel anti-leukemic medicine, we have prepared a Korean traditional medicine, named Hang-baek-Tang, which is composed of 8 kinds of anti-leukemic medicinal plants. The water extracts was examined anti-leukemic activity using the human leukemia cell line, HL-60 cells. HL-60 cells showed the growth inhibition and several apoptotic features, including DNA ladders, morphological changes, by treatment of the cells with Hang-Daek-Tang. We have observed that Hang-baek-Tang induced the activation of caspase-3, caspase-8 and caspase-9. Further molecular analysis demonstrated that Hang-baek-Tang induced cleavage of PARP and increase of hypodiploid (Sub-G1) population in flow cytometric analysis. These results indicate that Hang-baek-Tang has been considered to exert anti-leukemic activity through the procaspase-3 activation pathway.