Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/38154
標題: Ornithine decarboxylase attenuates leukemic chemotherapy drugs-induced cell apoptosis and arrest in human promyelocytic HL-60 cells
作者: Hsu, P.C.
洪慧芝
Hung, H.C.
Liao, Y.F.
Liu, C.C.
Tsay, G.J.
Liu, G.Y.
關鍵字: ornithine decarboxylase;cancer chemotherapeutic drug;apoptosis;cell;cycle;human-breast-cancer;topoisomerase-ii inhibitors;oxygen species;production;necrosis-factor-alpha;nf-kappa-b;cycle progression;dna-replication;s-phase;polyamine-biosynthesis;nih3t3 cells
Project: Leukemia Research
期刊/報告no:: Leukemia Research, Volume 32, Issue 10, Page(s) 1530-1540.
摘要: 
Ornithine decarboxylase (ODC), the rate-limiting enzyme of the polyamine biosynthetic pathway, plays an important role in cell cycle, tumor promotion and anti-apoptosis. In our previous studies, overexpression of ODC prevented apoptosis induced by tumor necrosis factor-alpha and methotrexate. We further investigated the apoptotic mechanisms of the cancer chemotherapeutic drugs, including etoposide (VP-16), paclitaxel (TAX) and cisplatin (CDDP), and the influences of ODC on apoptosis and cell cycle. Our results showed that the investigated drugs induced caspase-dependent apoptosis, the generation of reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential (Delta psi(m)) in HL-60 cells, all of which were reversed by putrescine, glutathione or N-acetyl-L-Cysteine. Overexpression of ODC prevented the cancer chemotherapeutic drugs-induced apoptosis, ROS generation and the disruption of Delta psi(m). After drug administrations, the decline of Bcl-2, cytochrome c release and caspases' activation were inhibited by ODC overexpression. In cell cycle, ODC overexpressed cells seemed to overcome the G1 arrest and G2/M arrest, caused by VP-16 and TAX, respectively, and kept on the cell cycle rolling. Overexpression of ODC increased the expression of Cyclin A, D, E and Cdk4 and the enzyme activity of Cdk1 and Cdk2 after the treatment of VP-16 and TAX, respectively. In conclusions, the cancer chemotherapeutic drugs-induced apoptosis is through ROS-related, mitochondria-mediated and caspase-dependent pathways. With higher ODC activity, cells are resistant to the cancer chemotherapeutic drugs-induced apoptosis and keep on the cell cycle rolling with the significant interference in G1/S arrest caused by VP-16 and G2/M arrest by TAX. (c) 2008 Elsevier Ltd. All rights reserved.
URI: http://hdl.handle.net/11455/38154
ISSN: 0145-2126
DOI: 10.1016/j.leukres.2008.01.017
Appears in Collections:生命科學系所

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