• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2453-2459
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• 2014

Ginsenoside Rg1 is one effective anticancer and antioxidant constituent of total saponins of Panax ginseng (TSPG), which has been shown to have various pharmacological effects. Our previous study demonstrated that Rg1 had anti-tumor activity in K562 leukemia cells. The aim of this study was designed to investigate whether Rg1 could induce apoptosis in TF-1/Epo cells and further to explore the underlying molecular mechanisms. Here we found that Rg1 could inhibit TF-1/Epo cell proliferation and induce cell apoptosis in vitro in a concentration and time dependent manner. It also suppressed the expression of EpoR on the surface membrane and inhibited JAK2/STAT5 pathway activity. Rg1 induced up-regulation of Bax, cleaved caspase-3 and C-PAPR protein and down-regulation of Bcl-2 and AG490, a JAK2 specific inhibitor, could enhance the effects of Rg1. Our studies showed that EpoR-mediated JAK2/STAT5 signaling played a key role in Rg1-induced apoptosis in TF-1/Epo cells. These results may provide new insights of Rg1 protective roles in the prevention a nd treatment of leukemia.

• 한국콘텐츠학회논문지
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• 제14권6호
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• pp.241-246
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• 2014

급성전골수구성 백혈병(Acute promyelocytic leukemia, APL)은 혈액암으로 치료가 쉽지 않을 뿐만 아니라 항암치료에 가장 효과가 좋다는 방사선 치료를 해도 오히려 정상세포에도 작용하여 부작용을 초래하게 된다. 본 연구에서는 전자선(EB)을 TNF-${\alpha}$와 같이 처리하였을 경우 정상세포와 암세포의 세포 죽음에 어떠한 영향을 미치는지 확인하였다. HL-60세포는 APL세포주로서 사용하였고 DMSO를 처리하여 분화시킨 HL-60세포는 정상과립구의 성질을 나타내어 정상대조군으로 이용하였다. 그 결과 TNF-${\alpha}$를 전자선을 처리한 HL-60세포에서만 세포독성효과를 나타내었고 이 과정에서 TNF-${\alpha}$는 caspase3를 활성화 시켜서 세포자멸사를 유도하여 세포가 죽음에 이르게 하였다. 결론적으로 TNF-${\alpha}$는 항암치료의 부작용을 없애기 위해 저농도의 전자선 치료 시 함께 사용하여 암 세포의 제거를 증가시켜 암의 치료효율을 높일 수 있는 유효물질로 사료된다.

• BMB Reports
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• 제31권6호
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• pp.560-564
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• 1998

Echinomycin-7 is an echinomycin derivative, Smethylated sulfonium perchlorate of echinomycin. We studied the in vitro cytotoxicity and in vivo antitumor activity of echinomycin-7 against P388 leukemia cells and compared the results with echinomycin. With respect to the cytotoxic effects, echinomycin-7 had cell line-dependent $IC_{50}$ values while echinomycin had similar values to several tumor cell lines. Also, in vivo antitumor activities were observed in tumor-bearing mice treated with both agents, which showed that echinomycin-7 had a broad therapeutic dose range. We also observed the apoptosis on leukemia cells treated with echinomycin-7 which exihibited the ladder pattern of DNA on electrophoresis. In addition to apoptosis, echinomycin-7 arrested $G_1/S$ phases of the cell cycle at the same time. We then examined the signaling pathway of echinomycin-7-induced apoptosis and showed that ERK of the MAP kinase family was activated and translocated into the nucleus by echinomycin-7 stimulation. This study suggests that echinomycin-7 acts as an antitumor agent through in vitro cytotoxicity and has in vivo antitumor activity against leukemia cells, and that the echinomycin-7- induced apoptosis might involve signal transduction via MAP kinases.

• 한국식품영양과학회지
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• 제35권10호
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• pp.1329-1335
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• 2006

AIDS로의 진행과정은 단순히 몇몇 기작에 의한 것이 아니라 여러 경로를 거쳐 발생하며 그 진행속도도 개개인에 따라 다양하게 나타나고 있다. 본 연구에서는 쥐 AIDS 모델을 이용하여 항산화호르몬으로 알려진 DHEAS의 면역조절 효과를 확인하고자 하였다. DHEAS의 투여는 LP-BM5 retrovirus 감염으로 인한 T와 B 임파구의 mitogenesis를 증가시켰으며 Th1/Th2 type cytokines의 발현에도 영향을 미쳤는데 주로 전사수준에서 작용한 것으로 생각된다/ 또한 retrovirus 감염으로 인한 간조직의 지질과산화 유발을 억제하여 조직 내의 항산화제인 vitamin E의 함량을 유지시킴으로 NF-kB의 활성화를 통한 retrovirus의 복제를 억제시켜 Th1/Th2 type cytokines의 불균형적인 발현을 저해하였을 것으로 여겨진다. 따라서 쥐 AIDS모델에 있어서 DHEAS의 면역조절 효과를 확인한 본 연구는 향후 HIV감염 이후 AIDS로의 진행 과정 시 항산화제의 역할과 기작 규명에 대한 가능성을 제시할 수 있을 것으로 생각된다.

• Journal of Yeungnam Medical Science
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• 제29권2호
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• pp.96-101
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• 2012

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the optimal curative treatment for acute myeloid leukemia (AML), but some patients develop bone marrow relapse due to remnant leukemia, and few patients develop extramedullary relapse without bone marrow relapse. Isolated extramedullary relapse (IMER) is defined as extramedullary relapse without bone marrow relapse. IMER has been reported in various sites, including the skin, soft tissue, and central nervous system(CNS). Isolated CNS relapse is relatively rare and is associated with poor prognosis due to the absence of an optimal treatment for it. Reported herein is a case involving an adult AML woman who suffered from isolated extramedullary relapse in the CNS after allogeneic HSCT. She was treated with intrathecal chemotherapy and whole-brain and spine radiotherapy, followed by systemic chemotherapy. She is currently well, with no evidence of leukemia recurrence for over six years.

• 동의생리병리학회지
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• 제19권4호
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• pp.913-921
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• 2005

In this study, we investigated gene expression patterns induced by Ailanthus altissima extract and compared it with Gleevec, a well-known anti-leukemia drug, in K562 chromic leukemia cells. Ailanthus altissima extract(100 ug/ml) and Gleevec(50 ug/ml) were treated to cells for 1h, 2h, 4h, and 16h and total RNA was extracted. Gene expressions were evaluated using cDMA microarray, in which 24,000 genes were spotted. Hierarchical clustering analysis showed that expression of genes included in two clusters were increased or decreased time dependently by both Ailanthus altissima extract and Gleevec. Genes included in another cluster were induced by Ailanthus altissima extract but not by Gleevec. In biological process analysis, expression of genes involved in apoptosis, growth arrest and DNA-damage were increased, but genes stimulating cell cycle were decreased. This study provides comprehensive comparison of the patterns of gene expression changes induced by Ailanthus altissima extract and Gleevec in K-562 leukemia cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10433-10438
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• 2015

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Aim and Objectives: This study investigated substitutions in the ATP synthase subunit 6 gene of mitochondrial DNA (mtDNA) as a potential diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Based on mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, approximately 465 bp of the ATP synthase subunit 6 gene were amplified and sequenced. Results: The sequencing revealed thirty-one mutations at 14 locations in ATP synthase subunit 6 of mtDNA in the ALL subjects. All were identified as single nucleotide polymorphisms (SNPs) with a homoplasmic pattern. The mutations were distributed between males and females. Novel haplotypes were identified in this investigation: haplotype (G) was recorded in 34% in diagnosed subjects; the second haplotype was (C) with frequency of 13% in ALL subjects. Neither of these were observed in control samples. Conclusions: These haplotypes were identified for the first time in acute lymphoblastic leukemia patients. Five mutations able to change amino acid synthesis for the ATP synthase subunit 6 were associated with acute lymphoblastic leukemia. This investigation could be used to provide an overview of incidence frequency of acute lyphoblastic leukemia (ALL) in Saudi patients based on molecular events.

• Journal of Life Science
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• 제9권1호
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• pp.9-13
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• 1999

Reduced thiols were important compounds for the maintenance of leukemia and lymphoma cell survival (and growth). In the course of examining the microenvirn-mental effects on lymphoma and leukemia cell growth, we found that cysteine suppressed apoptosis in these cells. In a present study, in order to investigate the role of cystein on the suppression of apoptotic cell death, we used CS21, P388, and L1210 cell lines. The addition of BSO, an inhibitor of glutathione synthase, induced apoptosis of these cells by blocking the cellular uptake of cysteine in CS21 cells. Although L1210 cells underwent apoptosis without thiol compounds, the addition of these compounds suppressed the apoptosis and promoted the growth or L1210 cells. When specific inhibitors of caspase3-like proteases, but not caspase1-like proteases, were activated during the L1210 cell apoptosis but the addition of thiol compounds suppressed the activation of caspase3-like proteases. These results suggest that reduced thiols including cysteine play an important role in the suppression of cell apoptosis by inhibiting the activation of caspase3-like proteases.

• Preventive Nutrition and Food Science
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• 제11권1호
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• pp.17-24
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• 2006

Methanolic and aqueous extracts from 37 seaweed species (10 green and 27 brown seaweeds) collected from Jeju Island coast were prepared at high ($70^{\circ}C$) and room ($20^{\circ}C$) temperatures and examined for cytotoxic activity against 4 tumor cell lines: U937 (human monoblastoid leukemia cell line), HL60 (human promyelocytic leukemia cell line), HeLa (woman cervical carcinoma cell line) and CT26 (mouse colon carcinoma line). Both MeOH extracts of Desmarestia tabacoides and Dictyota dichotoma possessed strong cytotoxic activities against all the tumor cell lines tested, but the aqueous extract exhibited no activity. On the other hand Ecklonia cava showed strong cytotoxic activities for the $20^{\circ}C$ aqueous extract against the three tumor cells except HeLa cell. Sagassum coreanum and Sagassum siliquastrum $20^{\circ}C$ aqueous extracts also exhibited strong cytotoxic activities against U937, HL60, HeLa cells. Even though green seaweeds showed less activity than brown seaweeds, $20^{\circ}C$ aqueous extracts of Codium contractum and Codium fragile exhibited strong cytotoxic activities against HL60 or CT26 cells, respectively.

• 약학회지
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• 제45권6호
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• pp.730-738
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• 2001

Apoptosis is a morphologically and biochemically distinct form of cell death that occurs in many different cell types in a wide variety of organisms. Ajbizzia julibrissin belonging the family Leguminosae has been used for the treatment of contusion, sore throat, amnesia, and insomnia in oriental traditional medicine. This study investigates whether the water extract off julibrissin induce apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Jurkat cells were increased inhibitions of cell viability in a concentration-dependent manner by A julibrissin. This herbal medicine also caused apoptosis as measured by cell morphology and DNA fragmentation. The capability oft julibrissin to induce apoptosis was associated with proteolytic cleavage of specific target protein such as poly (ADP-ribose) polymerase (PARP) protein suggesting the possible involvement of caspases. Our result skewed that Bcl-2 and Bax protein levels were not changed in all A julibrissin-treated groups compared to control group. These results suggest that A julibrissin-mediated apoptosis is independent with Bcl-2 related signaling pathway in this cells.