• 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.90.2-90.2
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• 2003

In a continuous effort to develop novel anticancer agents we newly synthesized and evaluated the antitumor activity of nucleoside analogues. One analogue, 4-[2-Chlor-6-(3-iodo-benzylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentanecarboxylic acid methylamide (LJ-331), has been shown to exert a potent inhibition of human cancer cell growth in vitro including human lung (A549), stomach (SNU-638) and leukemia (HL-60) cancer cells. Following mechanism of action study revealed that LJ-331 induces cell cycle arrest at the G$_1$ phase in HL-60 cells and evokes apoptotic phenomena such as an increase in DNA ladder intensity and chromatin condensation by a dose-and time-dependent manner. (omitted)

• 한국멀티미디어학회논문지
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• 제23권2호
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• pp.174-185
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• 2020

Leukemia induced death has been listed in the top ten most dangerous mortality basis for human being. Some of the reason is due to slow decision-making process which caused suitable medical treatment cannot be applied on time. Therefore, good clinical decision support for acute leukemia type classification has become a necessity. In this paper, the author proposed a novel approach to perform acute leukemia type classification using sequential neural network classifier. Our experimental result only cover the first classification process which shows an excellent performance in differentiating normal and abnormal cells. Further development is needed to prove the effectiveness of second neural network classifier.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5257-5261
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• 2013

The micronucleus frequency (MNF) in peripheral blood lymphocytes (PBL) is a biomarker of chromosomal damage and genome instability in human populations.The relationship of micronucleus frequency with prognosis of patients with acute leukemia is not clear. We therefore investigated MNF in mitogen-activated peripheral blood lymphocytes from patients with hematologic diseases and solid tumours. Patients included 50 with acute leukemia, 49 diagnosed with myelodysplastic syndrome (MDS), 54 with benign blood diseases, and 45 with solid tumours, examined with 50 healthy controls. The mean MNF was significantly higher in cases of hematologic diseases and solid tumor patients than in healthy controls (P<0.001). There was no evident difference between MNF in the acute leukemia ($7.15{\pm}2.18$) and solid tumor groups ($7.11{\pm}1.47$), but both were higher than in the MDS group ($5.12{\pm}1.29$) and benign blood diseases group ($3.08{\pm}1.08$). Taking 7.15‰, the average MNF of the acute leukemia group as standard, and dividing 50 cases of acute leukemia patients into high MNF group ($MNF{\geq}7.15$‰) and low MNF group (MNF<7.15‰). The overall response (complete remission + partial remission) rates of the low MNF group were significantly higher than in the high MNF group (P=0.001). The high MNF group further showed lower overall survival rates than the low MNF group. MNF expression and progression-free survival seemed to have a opposite relationship, with a correlation coefficient of -0.702. These data indicate that MNF in peripheral blood lymphocytes is important for evaluation of prognosis of acute leukemia patients, and it can reflect progression of disease to a certain degree.

• Biomolecules & Therapeutics
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• 제18권2호
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• pp.178-183
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• 2010

Costunolide is an active compound isolated from the stem bark of Magnolia sieboldii, and is considered a potential therapeutic for the treatment of various cancers. In this study, we investigated the underlying mechanism whereby costunolide induces the apoptosis of human leukemia cells. Using apoptosis analysis and quantitative reverse transcription-polymerase chain reaction (RT-PCR) results obtained during this study show that costunolide is a potent inducer of apoptosis and that it is triggered due to the premature activation of Cdc2. $G_1$-synchronized cells, which cannot undergo mitosis, were found to be more sensitive to costunolide, and Cdc2 mRNA levels were increased by costunolide treatment. Furthermore, the Cdk inhibitors, olomucine and butyrolactone I, were found to suppress costunolide-induced apoptosis. In addition, the PKC activator TPA rescued cells from cell death by costunolide, and this was prevented by the PKC inhibitor staurosporin. The present study suggests that costunolide induces the apoptosis of HL-60 leukemic cells by modulating cyclin-dependent kinase Cdc2.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.93-100
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• 2014

Background: Curcumin has has been reported to exert anti-inflammatory, anti-oxidation and anti-angiogenic activity in various types of cancer. It has also been shown to induce apoptosis in leukemia cells. We aimed to unravel the role of the redox pathway in Curcumin mediated apoptosis with a panel of human leukemic cells. Materials and Methods: In this study in vitro cytotoxicity of Curcumin was measured by MTT assay and apoptotic effects were assessed by annexin V/PI, DAPI staining, cell cycle analysis, measurement of caspase activity and PARP cleavage. Effects of Curcumin on intracellular redox balance were assessed using fluorescent probes like $H_2DCFDA$, JC1 and an ApoGSH Glutathione Detection Kit respectively. Results: Curcumin showed differential anti-proliferative and apoptotic effects on different human leukemic cell lines in contrast to minimal effects on normal cells. Curcumin induced apoptosis was associated with the generation of intracellular ROS, loss of mitochondrial membrane potential, intracellular GSH depletion, caspase activation. Conclusions: As Curcumin induces programmed cell death specifically in leukemic cells it holds a great promise as a future therapeutic agent in the treatment of leukemia.

• Natural Product Sciences
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• 제18권4호
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• pp.250-253
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• 2012

Phellodendri Cortex, phellodendron bark, has been used as a stomachic for intestinal function control and as an antimicro and anti-inflammatory agent. In this phytochemical study, eight compounds, berberine (1), palmatine (2), syringin (3), (+)-syringaresinol di-O-${\beta}$-D-glucopyranoside (4), salvadoraside (5), citrusin B (6), osmanthuside H (7), and kelampayoside A (8), were isolated from the bark of Phellodendron amurense. Their structures were elucidated by comparing spectroscopic data with reported values. Compounds 1 - 8 were evaluated for cytotoxic activity against HL-60 human promyelocytic leukemia cells in vitro. Among them, compounds 1 and 2 reduced the viability of HL-60 cells significantly, with $IC_{50}$ values of 26.0 and $18.5{\mu}M$, respectively.

• 생약학회지
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• 제40권2호
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• pp.118-122
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• 2009

Methanol extracts of Orostachys japonicus A. Berger (OAB) were found to exhibit apoptosis induction of HL60 human acute promyelocytic leukemia cells. Treatment of OAB exerted strong cytotoxicity against HL60 cells. OAB induced DNA fragmentation of HL60 cells in a dose dependent manner. Nitric oxide production were also increased in OAB-treated RAW264.7 macrophage cell lines. Treatment of OAB increased the expression of p53 and iNOS gene and the expression of p53, $NF-{\kappa}B$ and iNOS protein in cultured HL60 and RAW264.7 cells. These results suggest that OAB are effective on strong anti-cancer properties and can be useful as a chemo-preventive agents.

• 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.

• Archives of Pharmacal Research
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• 제18권6호
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• pp.396-401
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• 1995

As a part of trials to develop the antitumor agent from tannins isolated from plants, the antitumor activity of peduculagin, an ellagitannin, isolated from Alnus hirsuta var. microphylla was examined in vitro and in vivo. In vitro, the cytotoxicity was determined by 0.4% typanblue dye exclusion method. peduculagin showed the dose-dependent cytotoxicity against human chronic myelogenous leukemia (K-562), human promyelocytic leukemia (HL-60), mouse lymphoid neoplasm (P388), mouse lymphocytic leukemia (L1210) and mouse sarcoma 180(S180) cell lines. $ED_{50}\; values\; (ED_{50})$ of each cell line were 5.30, 0.92, 2.78, 9.35 and $1.38 \mug/ml$ respectively. The most sensitive cell line was HL-60. In vivo, pedunculagin was administered to ICR mouse with the doses of 50 and $100{\;}{\mu}g/ml$intraperitoneally once at 20 days before S180 inoculation. peduculagin showed the antitumor activity and its T/C ratio (%) was 120.82% in the group of both concentrations.

• Journal of Microbiology and Biotechnology
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• 제21권11호
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• pp.1193-1198
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• 2011

Encapsulation of biological material in the permiselective membrane allows to construct a system separating cells from their products, which may find biotechnological as well as biomedical applications in biological processes regulation. Application of a permiselective membrane allows avoiding an attack of the implanted microorganisms on the host. Our aim was to evaluate the performance of Bacillus subtilis encapsulated in an elaborate membrane system producing listeriolysin O, a cytolysin from Listeria monocytogenes, with chosen eukaryotic cells for future application in anticancer treatment. The system of encapsulating in membrane live Bacillus subtilis BR1-S secreting listeriolysin O was proven to exert the effective cytotoxic activity on eukaryotic cells. Interestingly, listeriolysin O showed selective cytotoxic activity on eukaryotic cells: more human leukemia Jurkat T cells were killed than human chronic lymphocytic B cells leukemia at similar conditions in vitro. This system of encapsulated B. subtilis, continuously releasing bacterial products, may affect selectively different types of cells and may have future application in local anticancer treatment.