Arginine deiminase enhances dexamethasone-induced cytotoxicity in human T-lymphoblastic leukemia CCRF-CEM cells. 2004

Eun-Joo Noh, and Sang-Wook Kang, and Yong-Jae Shin, and Sang-Hyun Choi, and Chan-Gil Kim, and In-Sun Park, and Denys N Wheatley, and Bon-Hong Min
Department of Pharmacology and BK21 Program for Medical Sciences, College of Medicine, Korea University, Seoul, Korea.

Since arginine deiminase (ADI; EC 3.5.3.6) inhibits cell proliferation by arresting cells in the G1 phase, we tested its synergistic effect on cell death induced by dexamethasone (DEX), which also induces apoptosis by G1 cell cycle arrest. ADI inhibited cell proliferation and induced apoptosis in human leukemic CEM cells in a dose-dependent manner. Simultaneous treatment with ADI and DEX showed synergistic effects on DNA fragmentation and LDH release. In addition, ADI exerted its anti-proliferative activity against DEX-resistant CEM cells. ADI suppressed expression of c-myc, a potential key regulator of cell proliferation and apoptosis, and increased expression of p27Kip1 cyclin-dependent kinase inhibitor. These results suggest that ADI efficiently increases the anti-cancer effect of DEX on human leukemic CEM cells through G1 cell cycle arrest involving downregulation of c-myc and upregulation of p27Kip1.

UI MeSH Term Description Entries
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006867 Hydrolases Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., ESTERASES, glycosidases (GLYCOSIDE HYDROLASES), lipases, NUCLEOTIDASES, peptidases (PEPTIDE HYDROLASES), and phosphatases (PHOSPHORIC MONOESTER HYDROLASES). EC 3. Hydrolase
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015459 Leukemia-Lymphoma, Adult T-Cell Aggressive T-Cell malignancy with adult onset, caused by HUMAN T-LYMPHOTROPIC VIRUS 1. It is endemic in Japan, the Caribbean basin, Southeastern United States, Hawaii, and parts of Central and South America and sub-Saharan Africa. ATLL,HTLV I Associated T Cell Leukemia Lymphoma,HTLV-Associated Leukemia-Lymphoma,HTLV-I-Associated T-Cell Leukemia-Lymphoma,Human T Lymphotropic Virus Associated Leukemia Lymphoma,Human T Lymphotropic Virus-Associated Leukemia-Lymphoma,Human T-Cell Leukemia-Lymphoma,Leukemia Lymphoma, Adult T Cell,Leukemia Lymphoma, T Cell, Acute, HTLV I Associated,Leukemia, Adult T-Cell,Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated,T Cell Leukemia Lymphoma, HTLV I Associated,T Cell Leukemia, Adult,T-Cell Leukemia, Adult,T-Cell Leukemia-Lymphoma, Adult,T-Cell Leukemia-Lymphoma, HTLV-I-Associated,Adult T-Cell Leukemia,Adult T-Cell Leukemia-Lymphoma,Adult T-Cell Leukemia-Lymphomas,Adult T-Cell Leukemias,HTLV Associated Leukemia Lymphoma,HTLV-Associated Leukemia-Lymphomas,HTLV-I-Associated T-Cell Leukemia-Lymphomas,Human T Cell Leukemia Lymphoma,Human T-Cell Leukemia-Lymphomas,Leukemia, Adult T Cell,Leukemia-Lymphoma, HTLV-Associated,Leukemia-Lymphoma, HTLV-I-Associated T-Cell,Leukemia-Lymphoma, Human T-Cell,Leukemia-Lymphomas, Adult T-Cell,Leukemia-Lymphomas, HTLV-Associated,Leukemia-Lymphomas, HTLV-I-Associated T-Cell,Leukemia-Lymphomas, Human T-Cell,Leukemias, Adult T-Cell,T Cell Leukemia Lymphoma, Adult,T-Cell Leukemia-Lymphoma, Human,T-Cell Leukemia-Lymphomas, Adult,T-Cell Leukemia-Lymphomas, HTLV-I-Associated,T-Cell Leukemia-Lymphomas, Human,T-Cell Leukemias, Adult
D016193 G1 Phase The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors. First Gap Phase,G1a Phase,G1b Phase,Gap Phase 1,First Gap Phases,G1 Phases,G1a Phases,G1b Phases,Gap Phase, First,Gap Phases, First,Phase 1, Gap,Phase, First Gap,Phase, G1,Phase, G1a,Phase, G1b,Phases, First Gap,Phases, G1,Phases, G1a,Phases, G1b
D016271 Proto-Oncogene Proteins c-myc Basic helix-loop-helix transcription factors encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis. L-myc Proteins,N-myc Proteins,c-myc Proteins,myc Proto-Oncogene Proteins,p62(c-myc),Proto-Oncogene Products c-myc,Proto-Oncogene Proteins myc,myc Proto-Oncogene Product p62,p62 c-myc,L myc Proteins,N myc Proteins,Proteins myc, Proto-Oncogene,Proto Oncogene Products c myc,Proto Oncogene Proteins c myc,Proto Oncogene Proteins myc,Proto-Oncogene Proteins, myc,c myc Proteins,myc Proto Oncogene Product p62,myc Proto Oncogene Proteins,myc, Proto-Oncogene Proteins,p62 c myc
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D050760 Cyclin-Dependent Kinase Inhibitor p27 A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2. CDK Inhibitor p27,CDKN1B Protein,CDKN4 Protein,Cyclin-Dependent Kinase Inhibitor 1B,p27 CDK Inhibitor,p27 Kip1 Protein,p27Kip1 Protein,CDK Inhibitor, p27,Cyclin Dependent Kinase Inhibitor 1B,Cyclin Dependent Kinase Inhibitor p27,Kip1 Protein, p27,p27, CDK Inhibitor

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