title: Arginine deiminase enhances dexamethasone-induced cytotoxicity in human T-lymphoblastic leukemia CCRF-CEM cells.
abstract: 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.
authors.affiliation: Department of Pharmacology and BK21 Program for Medical Sciences, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Noh
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Yong-Jae
authors.initials: YJ
authors.lastname: Shin
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Choi
authors.forename: Chan-Gil
authors.initials: CG
authors.lastname: Kim
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Park
authors.forename: Denys N
authors.initials: DN
authors.lastname: Wheatley
authors.forename: Bon-Hong
authors.initials: BH
authors.lastname: Min
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D006867:Hydrolases / Q000494:pharmacology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000201:enzymology* / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018797:Cell Cycle Proteins; D016271:Proto-Oncogene Proteins c-myc; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003907:Dexamethasone; D006867:Hydrolases; C019723:arginine deiminase