• Journal of Photoscience
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• v.9 no.2
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• pp.509-511
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• 2002

In this study, we investigated apoptotic cell death induced by photodynamic therapy using 5-aminolaevulinic acid (ALA-PDT) in human promyelocytic leukemia cells (HL-60). ALA-PDT induced apoptosis in HL-60 cells as confirmed by DNA agarose gel electrophoresis and nuclear staining with Hoechst 33342. The apoptotic cell death was inhibited by addition of broad-spectrum caspase inhibitor Z-Asp-CH$_2$-DCB, indicating that the apoptotic cell death was induced in a caspase-dependent manner. Actually, western blotting analysis revealed that caspase-3 was processed as early as 1.5 h after ALA-PDT. Cytoplasmic cytochrome c released from mitochondria was detected by western blotting. However, inhibitor of caspase-9, a cysteine protease located in the downstream of cytochrome c release, was not able to reduce the apoptotic cell death. Therefore, the mitochondrial apoptotic pathway was not involved in the ALA-PDT-induced apoptosis. On the other hand, it was found that ALA-PDT-induced apoptosis was clearly inhibited by pretreatment of caspase-8 inhibitor. These data suggest that caspase-8-mediated apoptotic pathway is important in ALA-PDT-induced cell death.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.157-161
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• 2003

The major ingredient of Persicae Semen is a cynogenic compound, amygdalin (D-mandelonitrile-$\beta$-gentiobioside). Controversial results on the anticancer activity of amygdalin were reported due to its conversion to its inactive isomer, neoamygdalin. In order to inhibit the epimerization of amygdalin, we used newly developed simple acid boiling method in preparation of Persicae Semen extract. HPLC analysis revealed most of amygdalin in Persicae Semen extract was active D-form. Persicae Semen extract was used to analyze its effect on cell proliferation and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. Persicae Semen extract was cytotoxic to HL-60 cells with $IC_{50}$ of 6.4 mg/mL in the presence of 250 nM of $\beta$-glucosidase. The antiproliferative effects of Persicae Semen extract appear to be attributable to its induction of apoptotic cell death, as Persicae Semen extract induced nuclear morphology changes and internucleosomal DNA fragmentation.

• Natural Product Sciences
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• v.18 no.4
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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.

• Archives of Pharmacal Research
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• v.28 no.9
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• pp.1047-1052
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• 2005

Two phenolic glucosides, eutigoside Band eutigoside C were isolated from the fresh leaves of Eurya emarginata. These two phenolic glucosides exerted a significant inhibitory effect on the growth of HL-60 promyelocytic leukemia cells. Furthermore, when the HL-60 cells were treated with eutigoside C, several apoptotic characteristics such as DNA fragmentation, morphologic changes, and increase of the population of sub-G1 hypodiploid cells were observed. In order to understand the mechanism of apoptosis induction by eutigoside C, we examined the changes of Bcl-2 and Bax expression levels. The eutigoside C reduced BcI-2 protein and mRNA levels, but slightly increased Bax protein and mRNA levels in a time-dependent manner. When we examined the activation of caspase-3, an effector of apoptosis, the eutigoside C increased the expression of active form (19-kDa) of caspase-3 and the increase of their activities was demonstrated by the cleavage of poly (ADP-ribose) polymerase, a substrate of caspase-3, to 85-kDa. The results suggest that the inhibitory effect of eutigoside C from E. emarginata on the growth of HL-60 appears to arise from the induction of apoptosis via the down-regulation of BcI-2 and the activation of caspase.

• BMB Reports
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• v.33 no.5
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• pp.402-406
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• 2000

In order to understand the role of AGP on the differentiation of promyelocytic leukemia cells, the AGP expression and its relation to cytokines were investigated during granulocytic or monocytic differentiation of HL-60 cells. When HL-60 cells were treated with all-trans-retinoic acid (ATRA) for 5 days, the cells were fully differentiated into granulocytes, and the AGP mRNA and protein levels were continuously increased up to 5 days in a dose- and time- dependent manner. However, in the case of the monocytic differentiation of HL-60 cells by tetradeanoyl phorbol acetate (TPA), the AGP gene expression was not induced. In addition, $IL-1{\alpha}$, $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNAs were also enhanced during granulocytic differentiation. These cytokine transcripts showed a peak level 3 days after the ATRA treatment. It decreased gradually thereafter. However, direct addition of recombinant cytokines ($IL-1{\beta}$, IL-6 and $TNF-{\alpha}$) and dexamethasone to the HL-60 cell cultures showed no AGP induction. These findings suggest that the AGP and proinflammatory cytokines are expressed in ATRA-treated promyelocytic cells. However, these cytokines do not act as autocrine inducers on AGP expression. This fact implies that the AGP expression during granulocytic differentiation of HL-60 cells is induced through a signal pathway different from hepatocyte signaling in inflammation.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.151-152
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• 2001

MCS-5A, novel Cdk inhibitor, has been reported that it has exerted cell cycle arrest action and apoptotic effect to the human promyelocytic leukemias cell. The purpose of this study is to verify these effects of MCS-5A on human promyelocytic leukemia (HL-60) cells and to clarify the action of mechanism on MCS-5A-inducing apoptosis.(omitted)

• BMB Reports
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• v.35 no.3
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• pp.337-342
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• 2002

Many components that are derived from medicinal or dietary plants possess potential chemopreventive properties. Curcumin, a yellow coloring agent from turmeric (Curcuma longa Linn, Zingiberaceae), possesses strong antimutagenic and anticarcinogenic activities. In this study, we have found that curcumin inhibits the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced nuclear factor ${\kappa}B$ (NF-${\kappa}B$) activation by preventing the degradation of the inhibitory protein $I{\kappa}B{\alpha}$ and the subsequent translocation of the p65 subunit in cultured human promyelocytic leukemia (HL-60) cells. Alternatively, curcumin repressed the TPA-induced activation of NF-${\kappa}B$ through direct interruption of the binding of NF-${\kappa}B$ to its consensus DNA sequences. Likewise, the TPA-induced DNA binding of the activator protein-1 (AP-1) was inhibited by curcumin pretreatment.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.212.1-212.1
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• 2003

2-Hydroxycinnamaldehyde is an active compound isolated from the Stem Bark of Cinnamomum cassia, a traditional oriental medicinal herb, which has been shown to inhibit tumor cell proliferation. In this study, we investigated the effects of 2-hydroxycinnamaldehyde on the cytotoxicity. induction of apoptosis and the putative pathways of its actions in human promyelocytic leukemia cells (HL-60). (omitted)

• Preventive Nutrition and Food Science
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• v.7 no.3
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• pp.250-254
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• 2002

The anticancer effects of leek (buchu in Korean) kimchi were evaluated in the human cancer cells: AGS gastric adenocarcinoma cells, HT-29 human colon adenocarcinoma cells and HL-60 leukemia cells. The leek kimchi (fermented for 6 days at 15$^{\circ}C$) was fractionated into 7 groups: methanol extract, hexane extract, methanol soluble extract MSE), dichloromethane (DCM) fraction (fr.), ethyl acetate fr., butanol fr. and aqueous fr. Most of the leek kimchi tractions inhibited the growth of AGS and HT-29 cancer cells in a dose dependent manner. In particular, the DCM fr. showed the highest inhibitory effect among the tractions. Treatment with the DCM fr. (0.1 mg/mL) reduced the survival rates of AGS and HT-29 cancer cells to 19% and 37% of the controls, respectively. Moreover the DCM fr. of the leek kimchi arrested G2/M phase in the cell cycle and induced apoptosis in HL-60 human promyelocytic leukemia cells. These results indicate that the leek kimchi exerted an anticancer effect on those human cancer cells, and that the DCM fr. arrested G2/M phase in the cell cycle and induced apoptosis in the leukemia cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1370-1374
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• 2005

The Tosyl-JM3 (TJM3) is a modified compound from one of 1,2,3,4-Tetra- hydroisoquinoline (THIQ) derivatives. The THIQs include potent cytotoxic agents that display a range of anti-tumor activities, antimicrobial activity, and other biological properties. In this study, we investigated the effect of TJM3 on the cytotoxicity, induction of apoptosis in human promyelocytic leukemia cells (HL-60 cells). TJM3 showed a significant cytotoxic activity in HL-60 cells (IC50 = approximately $60{\mu}g/m{\ell}$) after a 24 hr incubation. Treatment of HL-60 cells with TJM3 exhibited several features of apoptosis, including formation of DNA ladders in agarose gel electrophoresis, morphological changes of HL-60 cells with DAPI stain. Here we observed that TJM3 caused a decrease of procaspase-3 protein. Further molecular analysis demonstrated that TJM3 led to cleavage of poly(ADP-ribose) polymerase (PARP) by western blot and increase of hypodiploid (Sub-G1) population in the flow cytometric analysis. In conclusion, these above results indicate that TJM3 dramatically suppresses HL-60 cell growth and induces apoptosis. These data may support a possibility for the use of TJM3 in the prevention and treatment of leukemia.