• YAKHAK HOEJI
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• v.42 no.4
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• pp.345-352
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• 1998

Praecoxin A, an ellagitannin, purified from Alnus hirsuta var.microphlla was evaluated on the antitumor activity. Praecoxin A had the significant cytotoxicity to s ix tumor cell lines: human chronic myelogenous leukemia K-562, human promyelocytic leukemia HL-60, mouse leukemia P388, mouse lymphocytic leukemia L-1210, sarcoma-l8O, mouse lymphoma L5178Y except L-1210. And the most sensitive cell line was K-562 ($ED_{50}=2.43{\mu}g/ml$). The $ED_{50} of praecoxin A against HL-60, P388, L-1210, sarcoma7l8O and L5178Y were 6.28, 8.66, 10.00, 7.01, $9.32{\mu}g/ml$, respectively. Praecoxin A showed the increasing effect in life span by 36.8% on the 1st day after treatment of 10mg/kg in mice bearing sarcoma-180 tumor cells (ascitic form) via NCI (National Cancer Institute, U.S.A.) protocol in vivo assay. As a result, praecoxin A is considered to show the antitumor activity.

• Biomedical Science Letters
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• v.27 no.2
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• pp.95-98
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• 2021

The S100 family proteins act as inducers of cancer cell apoptosis and inflammatory mediators. This study examined the pro-apoptotic mechanism caused by S100A8 and S100A9 in human FIP1L1-PDGFRα-positive eosinophilic leukemia cells. S100A8 and S100A9 elicited the death of EoL-1 cells in a time and dose-dependent manner. The activation of PDGFRα was suppressed by a decrease in PDGFRα after treatment with S100A8 and S100A9. Cycloheximide, a translation inhibitor, suppressed PDGFRα expression from 1 h to 5 h, and a co-treatment with S100A8 and S100A9 boosted the decrease in expression. The phosphorylation and expression of STAT5 decreased after treatment with S100A8 and S100A9 in EoL-1 and imatinib-resistant (EoL-1-IR) cells. S100A8 and S100A9 induced the chemotaxis of EoL-1 cells but did not affect the chemoattraction of EoL-1-IR. These findings indicate the cell death mechanism due to S100 family proteins and the development of leukemia therapy using S100A8 and S100A9.

• Biomedical Science Letters
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• v.24 no.2
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• pp.134-137
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• 2018

S100A8 and S100A9 are involved in pathogenesis of cancer by induction or inhibition of cancer as well as inflammation. In this study, we investigated the association of S100A8 and S100A9 with pathogenesis of leukemia using human monocytic leukemia cells, THP-1. The expression of TLR4, which is a known receptor of S100A8 and S100A9, was examined by using flow cytometry and Western blotting. THP-1 cells have high surface and cytosol expression of TLR4. S100A8 and S100A9 suppressed the cell survival, and this suppression was found to be associated with apoptosis because they increased the number of apoptotic cells in a dose- and a time-dependent manners. However, S100A8 and S100A9 had no effect on the survival and apoptosis of monocytes isolated from the peripheral blood. We next examined the apoptotic effect of lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA), which are other ligands of TLR4, in THP-1 cells. Lipopolysaccharide had no effect on cell survival, but MPLA is effective on the cell apoptosis. These results suggest that S100A8 and S100A9 may regulate leukemia cell survival via TLR4, which is an essential receptor in the pro-apoptotic mechanism induced by S100A8 and S100A9. These findings may shed light on development of a possible therapeutic drug for leukemia treatment.

• Genomics & Informatics
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• v.8 no.4
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• pp.185-193
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• 2010

Histone deacetylation and demethylation are epigenetic mechanisms implicated in cancer. Studies regarding the role of modulation of gene expression utilizing the histone deacetylase inhibitor scriptaid and the demethylating agent 5-azacytidine in HL-60 leukemia cells have been limited. We studied the possibility of recovering epigenetically silenced genes by scriptaid and 5-azacytidine in human leukemia cells by DNA microarray analysis. The first group was leukemia cells that were cultured with 5-azacytidine. The second group was cultured with scriptaid. The other group was cultured with both agents. Two hundred seventy newly developed genes were expressed after the combination of 5-azacytidine and scriptaid. Twenty-nine genes were unchanged after the combination treatment of 5-azacytidine and scriptaid. Among the 270 genes, 13 genes were differed significantly from the control. HPGD, CPA3, CEACAM6, LOC653907, ETS1, RAB37, PMP22, FST, FOXC1, and CCL2 were up-regulated, and IGLL3, IGLL1, and ASS1 were down-regulated. Eleven genes associated with oncogenesis were found among the differentially expressed genes: ETS1, ASCL2, BTG2, BTG1, SLAMF6, CDKN2D, RRAS, RET, GIPC1, MAGEB, and RGL4. We report the results of our leukemia cell microarray profiles after epigenetic combination therapy with the hope that they are the starting point of selectively targeted epigenetic therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6549-6556
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• 2013

Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression and relapse, and thus represent a critical target for therapeutic intervention. Hence, it is extremely urgent to explore new therapeutic strategies directly targeting LSCs for acute myelogenous leukemia (AML) therapy. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), effectively inhibited human AML $CD34^+CD38^-$ cell proliferation in vitro culture in a dose-dependent manner while sparing normal hematopoietic stem and progenitor cells at physiologically achievable concentrations. Furthermore, ASP exerted cytotoxic effects on AML K562 cells, especially LSC-enriched $CD34^+CD38^-$ cells. Colony formation assays further showed that ASP significantly suppressed the formation of colonies derived from AML $CD34^+CD38^-$ cells but not those from normal $CD34^+CD38^-$ cells. Examination of the underlying mechanisms revealed that ASP induced $CD34^+CD38^-$ cell senescence, which was strongly associated with a series of characteristic events, including up-regulation of p53, p16, p21, and Rb genes and changes of related cell cycle regulation proteins P16, P21, cyclin E and CDK4, telomere end attrition as well as repression of telomerase activity. On the basis of these findings, we propose that ASP represents a potentially important agent for leukemia stem cell-targeted therapy.

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.565-583
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• 2011

Objectives : This study investigated the biochemical mechanisms of anti-proliferative and pro-apoptotic effects of the water extract of Dan-Seon-Tang (DST) in human leukemia U937 cells. Methods : U937 cells were exposed to DST and growth inhibition was measured by MTT assay. Results : Exposure of U937 cells to DST resulted in the growth inhibition in a concentration-dependent manner. This inhibitory effect was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies, increased populations of apoptotic-sub G1 phase and induction of DNA fragmentation. The induction of apoptotic cell death in U937 cells by DST was associated with up-regulation of death receptor 4 (DR4) and down-regulation of Bid, surviving and cellular inhibition of apoptosis protein-2 (cIAP-2) expression. DST treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant degradation of caspase-3 substrate proteins such as poly (ADP-ribose) polymerase (PARP), phospholipase (PLC)-${\gamma}1$, ${\beta}$-catenin and DNA fragmentation factor 45/inhibotor of caspase activated DNAse (DFF45/ICAD). Furthermore, apoptotic cell death by DST was significantly inhibited by caspase-3 specific inhibitor z-DEVD-fmk, demonstrating the important role of caspase-3. Conclusions : These findings suggest that herb prescription DST may be a potential chemotherapeutic agent for the control of human leukemia U937 cells; further study is needed to identify the active compounds.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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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.

• Journal of Microbiology and Biotechnology
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• v.22 no.2
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• pp.264-269
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• 2012

Recently, we reported that the synthetic Coprisin analog peptide 9-mer dimer CopA3 (consisted of all-L amino acid sequence) was designed based on a defensin-like peptide, Coprisin isolated from Copris tripartitus. The 9-mer dimer CopA3 (L-CopA3) had antibacterial activity and induced apoptosis in human leukemia cells via a caspase-independent pathway. In this study, all of amino acid sequences of L-CopA3 were modified to all D-form amino acids (DCopA3) to develop a more effective antimicrobial peptide. We investigated whether D-CopA3 had antimicrobial activities against pathogenic microorganisms and pro-apoptotic effects in human leukemia cells (U937, Jurkat, and AML-2). The synthetic peptide D-CopA3 had antimicrobial activities against various pathogenic bacteria and yeast fungus with MIC values in the 4~64 ${\mu}M$ range. Moreover, D-CopA3 caused cell growth inhibition, and increased the chromosomal DNA fragmentation and the expression of inflammatory cytokines, TNF-${\alpha}$ and IL1-${\beta}$, transcripts in human leukemia cells. The all-D amino acid peptide DCopA3 proved as effective as the L-CopA3 reported previously. These results provide the basis for developing D-CopA3 as a new antibiotic peptide.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1242-1253
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• 2004

Leukemia is a blood disease that occurs in the abnormal process of leukocyte maturation. Its main medical treatment is chemical therapy and bone medical transplant. But its treatments give rise to ill effects and sequela. At present, the cause of leukemia is not fully understood. But oriental concept of curing leukemia is the holistic thinking that emphasizes the unity, wholeness, and the relationship between the human organs, including western medical concept of blood cause. So it is estimated that holistic medical treatment in oriental medicine could present new medical way of curing leukemia. I read over the diary on struggles against leukemia, survey on the leukemia patients, and, medical charts in the oriental clinics that treated in the holistic way, and I interviewed the leukemia patients. With these materials, I classified the early main attacking symptoms according to the chief complaints of one hundred leukemia patients. With these results collected, I present new alternative treatment by oriental medical diagnosis. The chief early complaints that leukemia patients give are fatigue, enervation, cold, contusion, fever, high fever, sweating at sleep, myalgia, arthralgia, and dizziness, in order of main symptoms. Fatigue occurs mainly by spleen and stomach weakness and marrow shortage. So it is estimated that It is important to treat the spleen that is responsible for supplementing the marrow. Because the leukemia patients have anemia and hemorrhage, to treat the spleen is important for hematopoiesis and controlling blood. In case of cold, it penetrates into the body when the body is weak. So its treatment is to increase body's health. But the cause of fever is difficult to classify into outer cause and inner cause. But in case of children under 14 years old, fever is the main sypmptom. I think this is because children have the body with pure vital energy. Hemorrhage is thought to be the result of yin-lack and heat-miasma of spleen and stomach channels. Contusion occurs from the qi-weakness and the not-controlling-blood. Sweating at sleep is from the yin-weakness. It is found with all weak symptoms. Dizziness is from the yin-blood impairment. Weight-loss is from the marrow shortage. Myalgia and arthralgia is mainly from inner weakness, not outer maisma. Most leukemia patients have the idea that holistic treatment of leukemia could be of assistance and give help to the low immunity. So it is expected that holistic medical treatment could contribute to knowing the cause and treatment of leukemia, and give people reliability on oriental medical treatment, through the profound diagnosis of leukemia.

• Korean Journal of Pharmacognosy
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• v.30 no.1
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• pp.7-11
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• 1999

The present work was carried out to examine the effect of costunolide on the growth of several cells and characteristics of U-937 human leukemia-derived cell line. Costunolide produced a potent antitumor activity in vitro dependent on concentration against several tumor cells such as P-388, L-1210 leukemia and SNU-5 stomach cancer cells. However, it showed less cytotoxicity on normal cells such as Maccaccus rheus monkey kidney cells (MA-104) up to 200 ${\mu}M$ concentration. An effect of cell differentiation by costunolide was assessed by its ability to reduce nitroblue tetrazolium (NBT), and to induce phagocytosis of latex particles. In order to establish whether costunolide induces U-937 cells to differentiate toward macrophage or granulocyte, esterase activities was measured. Based on these results, we found that costunolide having cytotoxicity on U-937 human leukemia cells was explained through differentiation inducing activity.