• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.900-907
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• 2004

The antiproliferative effect of the water extract of the branch and root bark of Ulmi Pumilae Cortex(WEUPC) was investigated on the p53-negative human leukemia cell line (HL-60). A dose- and time-dependent inhibition of cell growth was observed; this effect appears to be due to induction of apoptosis. Involvement of oxidative stress is indicated by a dose-dependent increase in intracellular reactive oxygen species levels. In addition. anti-apoptic effect was observed in the cells simultaneously treated with WEUPC and the anti-oxidant N-acetylcysteine. WEUPC did not affect the anti-apoptotic Bcl-2 and the pro-apoptotic Bax, whereas p21/sup WAF1/CIPl/ was enhanced in a dose- and time-dependent fashion; this effect was partially inhibited by N-acetylcysteine. The increase in p21/sup WAF1/CIPl/ was accompanied by a parallel accumulation of cells in the G1 phase of the cycle. These results suggest that the p53-independent induction of p21/sup WAF1/CIP/ and the induction of apoptosis may mediate the anti proliferative effect of WEUPC at least in this study; on the basis of this observation, WEUPC could be proposed as an useful adjunct to the treatment of p53-deficient tumors, which are often refractory to standard chemotherapy.

• BMB Reports
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• v.45 no.3
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• pp.194-199
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• 2012

Autophagy has been suggested as a possible mechanism for non-apoptotic death despite evidence from many species that autophagy represents a survival strategy of cells under stress. From our previous findings that supranutritional doses of sodium selenite induced apoptosis in human leukemia cells, now we show autophagic cell death occurred after selenite exposure in HL60, suggested an alternative mechanism for the potential therapeutic properties of selenite. Additionally, Death-associated Protein Kinase (DAPK) performed a significantly increased expression during this process, concomitantly with gradually decreased phosphorylation at $Ser^{308}$. We further reveal that the up-regulation of DAPK which depends on selenite-activated ERK had no effect on autophagy. However, activation of DAPK via PP2A-mediated dephosphorylation at $Ser^{308}$ serves as a new strategy for autophagy induction. In conclusion, these results indicate that PP2A-mediated activated DAPK sensitizes HL60 cells to selenite, ultimately triggers autophagic cell death pathway to commit cell demise.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.120.3-121
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• 2003

Lycii Radicis Cortex, the root bark of Lycium chinense Miller (Solanaceae) is used in oriental medicine as a tonic and is reported to exhibit hypotensive, hypoglycemic, and antipyretic activity. Recently, we have isolated dihydro-N-caffeoyltyramine, a phenolic amide, from the Lycii Radicis Cortex. Treatment with dihydro-N-caffeoyltyramine significantly inhibited the proliferation of human leukemia cell lines HL-60 in a dose-dependent manner. We found also that the growth inhibition of HL-60 by dihydro-N-caffeoyltyramine is associated with induction of apoptosis of cells. (omitted)

• Food Science and Biotechnology
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• v.17 no.1
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• pp.188-190
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• 2008

In east Asia, the leaves of various Sasa species have been used in folk medicine for centuries. The effects of the methanolic extract and its subsequent fractions derived from the leaves of Sasa quelpaertensis Nakai on cell proliferation in human leukemia HL-60 cells were evaluated. The ethyl acetate fraction of this extract (ESQL) significantly reduced cell viability in a dose-dependent manner ($0-250\;{\mu}g/mL$). ESQL ($IC_{50}=24.8\;{\mu}g/mL$) exhibited growth inhibition comparable to the main constituent of green tea, epigallocatechin ($IC_{50}=26.2\;{\mu}g/mL$), which was used as a positive control. ESQL treatment induced apoptosis, which was confirmed by the presence of nuclear condensation and annexin V-staining. These results demonstrate that ESQL contains chemopreventive phytochemicals that may be useful in neutraceutical applications.

• Proceedings of the PSK Conference
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• 2002.10a
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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.

• Archives of Pharmacal Research
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• v.29 no.11
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• pp.1032-1041
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• 2006

Extracellular adenosine 5'-triphosphate (ATP) affects the function of many tissues and cells. To confirm the biological activity of ATP on human myeloid leukemic cells, F-36P and HL-60, cells were treated with a variety of concentrations of ATP. The stimulation with extracellular ATP induced the arrest of cell proliferation and cell death. from the analysis of Annexin-V staining and caspase activity by flow cytometry. The Annexin-V positive cells in both cell lines were dramatically increased following ATP stimulation. The expression of P2 purinergic receptor genes was confirmed, such as P2X1, P2X4, P2X5, P2X7 and P2Y1, P2Y2, P2Y4, P2Y5, P2Y6, P2Y11 in both leukemic cell lines. Interestingly, ATP induced intracellular calcium flux in HL-60 cells but not in F-36P cells, as determined by Fluo-3 AM staining. Cell cycle analysis revealed that ATP treatment arrested both F-36P and HL-60 cells at G1/G0. Taken together, these data showed that extracellular ATP via P2 receptor genes was involved in the cell proliferation and survival in human myeloid leukemic cells, HL-60 and F-36P cells by the induction of apoptosis and control of cell cycle. Our data suggest that treatment with extracellular nucleotides may be a novel and powerful therapeutic avenue for myeloid leukemic disease.

• Advances in Traditional Medicine
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• v.9 no.2
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• pp.186-191
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• 2009

Eriocaulon sieboldianum (ES) is used in traditional oriental medicine for various medicinal purposes including headache, toothache, and inflammation. However, the anti-cancer effect of the ES is still not fully understood. In the present study, the human leukemia cell line HL-60 was used to characterize the apoptotic effects of ES. ES induced cytotoxicity of HL-60 cells in a dose- and time-dependent manner. ES induced the generation of reactive oxygen species, and the release of cytochrome c in a dose-dependent manner. In addition, we showed that ES-induced apoptosis was accompanied by activation of caspase-3. Taken together, our results demonstrate that ES possesses anti-cancer activity in HL-60 cells.

• Journal of Nutrition and Health
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• v.36 no.8
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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.

• Journal of Food Hygiene and Safety
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• v.24 no.1
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• pp.38-45
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• 2009

The differentiation of leukemia cells into mature cells is a major target of the human leukemia therapy. As differentiated leukemia cells lose their proliferative and tumor-forming abilities, differentiation inducers may be useful for the treatment of leukemia. In this study, the experiments were designed to determine whether diallyl disulfide (DADS) regulates expressions of tumor suppressor protein PTEN (phosphatase and tension homologue) in HL60 cells. DADS causes upregulation of PTEN in a time- and dose-dependent manner, which was correlated with decrease of phospho-Akt level. These results suggest that DADS induces upregulation of PTEN in human leukemia cells. These results suggest that DADS may be a useful anticancer agent for management of human leukemia.

• Journal of radiological science and technology
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• v.29 no.4
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• pp.285-291
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• 2006

During cancer therapy, gamma-ray irradiation and treatment of anti-cancer chemicals destroy the normal cells as well as cancer cells. In this study, we investigated the effect of epigallocathechin-gallate(EGCG) extracted from green tea, which is known to have anti-cancer and anti-oxident activities, in order to find out the feasible method to protect the normal cells and to kill the cancer cells efficiently. We investigated the effect of EGCG on the leukemia cell growth and cell necrosis, especially when treated along with gamma radiation. The EGCG inhibited the leukemia cell, HL-60, growth at the appropriate concentration while it exhibited no influence on the normal cell growth. More significantly, it enhanced leukemia cell necrosis when its treatment was combined with gamma irradiation. Simultaneous treatment of EGCG and gamma radiation increased leukemia cell necrosis up to 35% compared with separate treatments. These results suggest that drinking of green tea or co-treatment of EGCG during gamma irradiation therapy may result in better prognosis through enhancement of the tumor cell necrosis and protection of the normal cells.