• IMMUNE NETWORK
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• 제9권2호
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• pp.35-40
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• 2009

Although Rap GTPases of the Ras family remained enigmatic for years, extensive studies in this decade have revealed diverse functions of Rap signaling in the control of cell proliferation, differentiation, survival, adhesion, and movement. With the use of gene-engineered mice, we have uncovered essential roles of endogenous Rap signaling in normal lymphocyte development of both T- and B-lineage cells. Deregulation of Rap signaling, on the other hand, results in the development of characteristic leukemia in manners highly dependent on the contexts of cell lineages. These results highlight crucial roles of Rap signaling in the physiology and pathology of lymphocyte development.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.206.1-206.1
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• 2001

• 동의생리병리학회지
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• 제21권4호
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• pp.940-945
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• 2007

We have examined the induction of HL-60 cell differentiation by treatment of 2-chloromethyl-1-dihydroxyphosphinyl pyrrolidine(2C-1DPP), which is derivative of piperidine and pyrrolidine by ${\alpha}-phosphoramidoakylation$ reaction. It was observed that HL-60 cell proliferation was dose- and time-dependently inhibited by treatment with 2C-1DPP. 2C-1DPP treatment caused a significant change in NBT reduction and enhanced ATRA-induced NBT reduction. Treatment of 2C-1DPP to HL-60 cells increased only CD11b expression in the cells, and also increased markedly G0/G1 stage arrest of HL-60 cells. These results can suggest that 2C-1DPP induced the differentiation of HL-60 cells to granulocytes lineage and enhanced ATRA-induced differentiation. Moreover, DNA expression levels of p27 were up-regulated during 2C-1DPP-dependent HL-60 cell differentiation. Our results suggest that 2C-1DPP have potential as a therapeutic agent in human leukemia.

• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.79-86
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• 2001

Recent clinical studies have shown that a high proportion of patients with acute promyelocytic leukemia (APL) achieve complete remission after treatment with all-trans retinoic acid (ATRA). However, most patients who receive continuous treatment with ATRA relapse and develop ATRA-resistant leukemia. Dendritic cells (DCs) are important antigen-presenting cells in the development of antileukemic T-cell responses. In this study, we investigated the strategies to overcome ATRA resistance of APL cells by inducing the differentiation of DCs from human leukemic cell lines for the developtment of adoptive immunotherapy. CD83 was used as a mature DC marker in this study and the expression of CD83 mRNA was determined by RT-PCR method. The promyelocytic leukemic cell line HL-60, B lymphoblast cell lines RPMI 7666 and NC-37 could be induced to dendritic cells in vitro. Treatment of HL-60 with phorbol 12-myristate 13-acetate (PMA) resulted in the expression of myeloid-related DC phenotypes, while treatment of RPMI 7666 with fms-like tyrosine kinase 3 ligand (Flt3-ligand, FL) and treatment of NC-37 with PMA and FL led to the expression of lymphoid-related DC phenotypes. In conclusion, myeloid-related DC phenotypes and lymphoid-related DC phenotypes could be generated from HL-60, NC-37 and RPMI 7666 cell lines, respectively. These DC phenotypes can potentially be used to generate antileukemic T cells in vitro for adoptive immunotherapy.

• Molecules and Cells
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• 제38권6호
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• pp.482-495
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• 2015

Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1-phosphate plays a role in cell survival/proliferation. The lipids are metabolized by the specific enzymes, and each metabolite could be again returned to the original form by the reverse action of the different enzyme or after a long journey of many metabolizing/synthesizing pathways. In addition, the metabolites may serve as reciprocal biomodulators like the rheostat between ceramide and sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the subcellular localization and the downstream signal in a specific subcellular organelle should be clarified to understand the pathobiological significance of sphingolipids when extracellular stimulation induces a diverse of cell functions such as cell death, proliferation and migration. In this review, we focus on how sphingolipids and their metabolizing enzymes cooperatively exert their function in proliferation, migration, autophagy and death of hematopoetic cells, and discuss the way developing a novel therapeutic device through the regulation of sphingolipids for effectively inhibiting cell proliferation and inducing cell death in hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma.

• 생명과학회지
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• 제16권5호
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• pp.759-766
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• 2006

급성 전골수성 백혈병은 염색체 전위의 결과로 생긴 PML/RAR$({\alpha})$ 융합 단백의 과발현으로 영향을 받은 전골 수세포의 분화 정지로 발생하는 골수성 백혈병의 일종이다. 삼산화 비소는 세포고사를 유발하여 급성전골수성 백혈병의 관해를 유도한다는 것이 밝혀졌으나 이 약제에 대한 감수성이 다양하여 고형암에 적용하기에는 제한점이 있다. All-trans-retinoic acid (ATRA)에 감수성인 NB4 세포주와 내성인 UF-1 세포주 모두에 삼산화 비소가 세포고사를 유도하였다. 백혈병 세포주를 삼산화 비소로 처리하여, 세포내 GSH 농도가 낮아지고 세포고사의 감수성이 높아지는 상관관계를 찾았으며 전골수성 암세포를 수지상 세포 표면 표식자를 가진 세포로 분화시켰다. ATRA에 대한 감수성인 세포주와 내성인 세포주의 삼산화 비소에 대한 반응의 차이를 이해하고, 전골수 세포가 수지상 세포로 분화하는 과정을 규명한다면, 삼산화 비소에 의한 전골수성 백혈병의 완전관해의 기전을 밝힐 수 있고 또한 임상적용을 확대할 수 있을 것이다.

• 한국동물학회지
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• 제34권4호
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• pp.469-478
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• 1991

The CALLA on the surface of leukemic cell lines, recognized by our monoclonal antibody. KP-22(IgG1, K) was one of cell surface glycoproteins having moi. wt. of approximately 100,000 dalton, and could be shed in spent medium or endocytosed when binding the cognate antidoby, KP-22. In the presence of cognate antibodies, 60% of CALLAS recogniEed by KP-22 MAs were modulated and cleared from the cell surface during 24 hrs, and approximaetely 35% of them was endocytosed and 25%, was shed in spent medium. The reappearance of the membrane CALLA after modulation by the KP-22 required at least 6 hours and supposed to be newly synthesized molecules.

• Archives of Pharmacal Research
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• 제21권1호
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• pp.41-45
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• 1998

Hypericin, a photosensitizing plant pigment, was found to be a potent inducer of differentiation of human myeloid leukemia U-937 cells. At a concentration of $0.2{\mu}M$, hypericin exhibited 50% growth inhibition. An effect on cell differentiation by hypericin was assessed by its ability to induce phagocytosis of latex particles, and to reduce nitroblue tetrazolium (NBT). Approximately 51% of $0.2{\mu}M$ hypericin-treated cells were stained with NBT and 63% showed phagocytic activity. In order to establish whether hypericin induces differentiation of U-937 cells to macrophage or granulocyte, esterase activities and cell sizes were measured. When U-937 cells were treated with $0.2{\mu}M$ and $0.15{\mu}M$ of hypericin, the .alpha.-naphthyl acetate esterase activity was increased by 38.4% and 48.1%, respectively, but naphthol AS-D chloroacetate esterase activity was not influenced. The size of hypericin-treated cells in terms of cell mass was larger than that observed in untreated cells as determined by flow cytometry. Protein kinase C (PKC) inhibitor, NA-382, decreased the NBT reducing activity of hypericin, whereas a cAMP-dependent protein kinase A (PKA) inhibitor, H-89, did not show any influence on the differentiations. These results indicate that hypericin triggers differentiation toward monocyte/macrophage lineage by PKC stimulation.

• 한국약용작물학회지
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• 제10권4호
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• pp.237-242
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• 2002

It was found that the purified extract from A. gigas Nakai (polysaccharide, M.W., 25 kD) controled differentiating human ES cells. Its optimal supplementation concentration was decided as 0.8 $({\mu}g/ml)$ to efficiently control the differentiation. It also enhanced the cell growth, compared to the control. However, most widely used and commercially available differentiating agent, Leukemia Inhibitory Factor (LIF) negatively affected on the cell growth even though it controls the differentiation of ES cells, down to 40-50 % based on morphological observation and telomerase activity. It was presumed that the extract first affected on cell membrane and resulted in controlling signal system, then amplify gene expression of telomere, which enhanced the telomerase activity up to three times compared to the control. LIF only increased the enzyme activity up to two times. It was confirmed that the extract from A. gigas Nakai could be used for substituting currently used differentiation controlling agent, LIF from animal resources as a cheap plant resource and not affecting the cell growth. It can broaden the application of the plants not only to functional foods and their substitutes but also to fine chemicals and most cutting-edge biopharmaceutical medicine.

• 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.166.3-167
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• 2003

Helenalin, a cell-permeable pseudoguainolide sesquiterpene lactone, is a potent anti-inflammatory agent that inhibits $NF-{\kappa}B$ DNA binding activity by selectively alkylating the p65 subunit of $NF-{\kappa}B$. Transcription factors such as $NF-{\kappa}B$ provide powerful target of drugs to use in the treatment of cancer. Human promyelocytic leukemia HL-60 cells are differentiated into monocytic or granulocytic lineage when treated with 1,25-dihydroxyvitamin $D_3{\;}[1,25-(OH)_2D_3]$ or all-trans-retinoic acid (ATRA), respectively. (omitted)